Omne vivum ex ovo: the oocyte reprogramming and remodeling activities

in Reproduction
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Helena FulkaInstitute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic
Institute of Animal Science, Prague, Czech Republic

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Pasqualino LoiFaculty of Veterinary Medicine, University of Teramo, Teramo, Italy

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Marta CzernikFaculty of Veterinary Medicine, University of Teramo, Teramo, Italy

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Azim SuraniThe Gurdon Institute, Cambridge, UK

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Josef FulkaInstitute of Animal Science, Prague, Czech Republic

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Correspondence should be addressed to H Fulka; Email: helena.fulkova@iem.cas.cz
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In brief

Understanding the establishment of post-fertilization totipotency has broad implications for modern biotechnologies. This review summarizes the current knowledge of putative egg components governing this process following natural fertilization and after somatic cell nuclear transfer.

Abstract

The mammalian oocyte is a unique cell, and comprehending its physiology and biology is essential for understanding fertilization, totipotency and early events of embryogenesis. Consequently, research in these areas influences the outcomes of various technologies, for example, the production and conservation of laboratory and large animals with rare and valuable genotypes, the rescue of the species near extinction, as well as success in human assisted reproduction. Nevertheless, even the most advanced and sophisticated reproductive technologies of today do not always guarantee a favorable outcome. Elucidating the interactions of oocyte components with its natural partner cell – the sperm or an ‘unnatural’ somatic nucleus, when the somatic cell nucleus transfer is used is essential for understanding how totipotency is established and thus defining the requirements for normal development. One of the crucial aspects is the stoichiometry of different reprogramming and remodeling factors present in the oocyte and their balance. Here, we discuss how these factors, in combination, may lead to the formation of a new organism. We focus on the laboratory mouse and its genetic models, as this species has been instrumental in shaping our understanding of early post-fertilization events.

Abstract

In brief

Understanding the establishment of post-fertilization totipotency has broad implications for modern biotechnologies. This review summarizes the current knowledge of putative egg components governing this process following natural fertilization and after somatic cell nuclear transfer.

Abstract

The mammalian oocyte is a unique cell, and comprehending its physiology and biology is essential for understanding fertilization, totipotency and early events of embryogenesis. Consequently, research in these areas influences the outcomes of various technologies, for example, the production and conservation of laboratory and large animals with rare and valuable genotypes, the rescue of the species near extinction, as well as success in human assisted reproduction. Nevertheless, even the most advanced and sophisticated reproductive technologies of today do not always guarantee a favorable outcome. Elucidating the interactions of oocyte components with its natural partner cell – the sperm or an ‘unnatural’ somatic nucleus, when the somatic cell nucleus transfer is used is essential for understanding how totipotency is established and thus defining the requirements for normal development. One of the crucial aspects is the stoichiometry of different reprogramming and remodeling factors present in the oocyte and their balance. Here, we discuss how these factors, in combination, may lead to the formation of a new organism. We focus on the laboratory mouse and its genetic models, as this species has been instrumental in shaping our understanding of early post-fertilization events.

Introduction

Mammalian development is a complex process that starts with fertilization when two gametes, the sperm and the egg, transform into a zygote. While the sperm contributes half of the genetic and epigenetic information, the egg, in addition, provides practically all the building blocks for the initial phases of embryonic development. Using a set of experiments based on the technique of nuclear transfer and other micromanipulations and a focused exploration of the oocyte biology, we are beginning to understand which oocyte components and parts are necessary for each step, which leads to the establishment of post-fertilization totipotency and successful development.

In contrast to the state of terminal differentiation of gametes, totipotency is the ability of a given cell to give rise to all cell types of an organism and is inherent to embryos. Totipotency is established at fertilization and is restricted to early cleavage stage embryos (Tarkowski 1959, Zhang et al. 2018, Krawczyk et al. 2021, Maemura et al. 2021). Totipotency results from two processes: remodeling and reprogramming of the parental genomes. While reprogramming is generally understood in terms of the gene expression programs, the remodeling involves rather structural alterations to the genomes. Therefore, the remodeling includes changes related to the general appearance of the formed nucleus and/or changes to the DNA structure, which might or might not lead to a change in a gene expression program. As the sperm contributes only a limited amount of material, both of these processes are inherently under the influence of egg components until the embryo activates its genome and starts producing its transcripts.

Although the egg is perfectly equipped to reprogram and remodel its natural partner, the spermatozoon, it is also capable of reprogramming and remodeling somatic cell nuclei so that a new individual is born. Even in the case when a somatic cell is used to supply the genetic material, practically, all the building blocks and other factors are provided by the egg. However, in this case, the somatic nucleus can, and very often does, retain part of its cellular memory, and some specific regions of the genome were shown to be resistant to reprogramming (Matoba et al. 2014, Hörmanseder et al. 2017). Still, compared to other methods such as exposure to extracts or the induction of the OSKM (OCT4 (POU5F1), SOX2, KLF4 and c-MYC) transcription factors (Takahashi & Yamanaka 2006), the egg is generally regarded as the most efficient milieu capable of altering the fate of a nucleus leading to a full-term development; for review see Gurdon & Melton 2008, Zhao et al. 2021. Next, we will describe the unique biology of the female germ cell and focus on the components that likely contribute to reprogramming and remodeling as both of these activities are associated with the totipotency establishment.

Biology of oocytes and eggs

One of the unique features of the oocyte is its size, which reaches approximately 75 µm in mice or about 120 µm in humans or cattle (Wassarman & Josefowicz 1978, Levi et al. 2013). Throughout the growth phase, oocytes accumulate vast amounts of different materials, including proteins and other molecules, later used by the embryo. Accordingly, the oocyte nucleus, the germinal vesicle (GV), is enormous. Correspondingly to the size, the GV contains substantial nuclear bodies, as evident by the appearance of the nucleolus (the nucleolus-like body, NLB). Only when oocytes reach their full size and undergo a dramatic chromatin reorganization, they become competent to support development (Zuccotti et al. 2002, Inoue et al. 2008). The process of chromatin reorganization is termed as NSN-to-SN transition. The chromatin rearranges from a dispersed configuration (NSN, non-surrounded nucleolus) to a more condensed state during this process and the chromatin comes close to the NLB (SN, surrounded nucleolus). Based on a series of SN and NSN GV transfer experiments performed by Inoue and colleagues in 2008, the authors suggested that only germinal vesicles of the SN-type, but not of the NSN-type, oocytes contain factors required for successful development (Inoue et al. 2008). When oocytes start to mature, i.e. they re-initiate meiosis, the nuclear envelope breaks down (GVBD – germinal vesicle breakdown), the chromosomes condense. The GV content with intranuclear organelles becomes dispersed in the cytoplasm. Although the final phases of oocyte growth are accompanied by a marked reduction in transcriptional activity (Moore & Lintern-Moore 1974, Bouniol-Baly et al. 1999), resumption of meiosis and meiotic maturation triggers the translation of specific maternal mRNAs, for review see Conti & Franciosi 2018. Therefore, developmental competence depends on both nuclear and cytoplasmic maturation. The fertilization occurs at metaphase II when the oocytes, now typically referred to as the eggs, are ovulated. The female meiosis is typified by an asymmetric division when most of the accumulated materials are retained by the egg cell. Only a minor part, together with oocyte chromosomes, is lost in the form of the first and second polar bodies.

The same stage of the oocyte, i.e. metaphase II, is also used for the somatic cell nuclear transfer (SCNT) – a procedure when the meiotic spindle with attached chromosomes is removed, giving rise to a so-called cytoplast, and replaced by a nucleus of a somatic cell. The goal of SCNT is to recapitulate or mimic the natural events occurring at fertilization (Fig. 1).

Figure 1
Figure 1

The scheme summarizes the current knowledge on the changes occurring with the oocyte growth around the time of fertilization and early embryogenesis. During the growth phase, oocytes develop some specific features: they accumulate specific histone variants and establish oocyte-specific 3D genome features. At the same time, the sperm exhibits some unique features. These parental-specific genome features are generally not reconciled before the embryonic eight-cell stage following fertilization. The reprograming and remodeling activity is typically confined to the nucleus at stages with a low MPF activity. It gradually disappears with the loss of totipotency.

Citation: Reproduction 165, 3; 10.1530/REP-22-0124

Although the transition of NSN-to-SN chromatin distribution, which accompanies the gain of the developmental competence of oocytes, has been described decades ago, only with the advent of modern low-input technologies, we are beginning to appreciate the genome organization of oocytes in 3D space. The organization of the genome and its interactions with different nuclear components are overly complex. At the basic level, chromatin can be divided into the active euchromatin, which replicates early during S-phase and mid-to-late S-phase, which replicates inactive heterochromatin (Chagin et al. 2010, Heinz et al. 2018). In most cells, the heterochromatin tends to localize to the nuclear periphery, i.e. adjacent to the nuclear envelope, or to the nucleolus; for review, see Bizhanova & Kaufman 2021. More refined mapping of the 3D genome organization by high-resolution chromosome conformation capture (Hi-C) showed that, at the megabase scale, the genome is organized into two compartments characterized by the frequency of interactions: the active A and the inactive B compartment (Fortin & Hansen 2015). The organization of chromosomes to topologically associated domains (TADs) has been identified at an even more refined level, with cohesin and CCCTC-binding factor (CTCF) having the crucial role in defining TADs and their boundaries (Wutz et al. 2017, Szabo et al. 2019). Sequences from one TADs tend to interact among themselves, i.e. in cis, rather than with different sequences from another TAD (Pope et al. 2014, Szabo et al. 2019). The final higher-order organization of chromatin is the loops, for review see Holwerda & De Laat 2012, Hansen et al. 2018. In NSN GV oocytes, all three levels of chromatin organization, i.e. loops, TADs and compartments, were found. Still, as the oocytes transit to the SN stage, the strength of the loops, TADs and compartments decreases and the TADs and compartments are lost at the metaphase II stage (Du et al. 2017, Flyamer et al. 2017). The chromatin organization of the egg is not specific as mitotic chromosomes also lack TADs (Naumova et al. 2013). Not surprisingly, as the oocyte chromatin at the SN stage is clustered around NLBs, typical lamina-associated domains (LADs) were not found (Borsos et al. 2019). This finding was obtained by the DamID method using the lamin B1-Dam fusion construct. DamID is a bacterial DNA adenine methylase, which can mark the DNA sequences that come into proximity to the protein structure of interest, the nuclear lamina (Kind et al. 2013). Although the method is not without its limitations, the obtained results only underscore the microscopic observations and the idea of the oocyte chromatin detachment from the nuclear envelope. These chromatin features change after fertilization with the process of reprogramming and remodeling.

When compared to somatic cells, the oocyte chromatin is quite unique. The basic chromatin proteins are histones. These are part of the nucleosome, composed of two copies of each histone H2A, H2B, H3 and H4 and approximately 146 bps of DNA. It is now well established that histones are subjected to post-translational modifications (PTMs). Although the oocyte genome exhibits histone modifications, which are not grossly different from those in somatic cells, there are some specific features. One exception seems to be the presence of unusually large domains associated with the H3K4me3 histone modification which occupy nearly one-fourth of the mouse oocyte genome (Dahl et al. 2016, Zhang et al. 2016). However, this feature does not seem to be conserved among mammals (Xia et al. 2019). Apart from the regular histones, several histone variants have been identified, and some of these are highly enriched in germ cells or are germ cell-specific. A typical example of such a variant is the histone H3.3, which differs from the canonical H3 histones only by four amino acids and is continuously exchanged and replaced in the oocytes by the histone chaperone HIRA in the absence of replication (Hake & Allis 2006, Nashun et al. 2015). Additional histone variants include TH2A and TH2B, enriched in male and female germ cells. All the mentioned histone variants have been experimentally shown to aid the reprogramming of somatic cells and might also have a role in totipotency establishment (Shinagawa et al. 2014, Wen et al. 2014). The same beneficial effect has also been described for another oocyte histone variant, the linker histone H1foo, which further packages and stabilizes the nucleosomes (Tanaka et al. 2001, Kunitomi et al. 2016).

Reprogramming

Understanding the cellular reprogramming process and the factors responsible has a high potential for various areas, including regenerative medicine. Although different protocols have been developed over the last decades, it has been shown that the combination of other factors present in the female germ cells around the time of fertilization provides an unrivaled reprogramming milieu. This is demonstrated by the efficiency of the somatic cell nuclear transfer (SCNT), a procedure during which the egg´s chromosomes are removed and replaced by the genetic information of a somatic cell. Despite a significant effort, the specific factors and their combinations remain elusive. Nevertheless, the primary focus has been placed on the chromatin as, in essence, the reprogramming leads to changes in gene expression. Besides the specific histone variants highly enriched in oocytes, transcription factors and ATP-dependent chromatin remodeling complexes are likely also involved (Fu et al. 2019). These might act either directly or indirectly on the parental genomes to facilitate the transformation of the fully differentiated gametes to totipotency and include factors such as SMARCA4/BRG1, ATP-dependent chromatin remodeler, or SIN3A, an interacting partner of histone deacetylases (Bultman et al. 2006, Jimenez et al. 2015). Several other promising candidates for the induction of the early embryonic transcriptional program and totipotency were identified. These include DUX, encoded by Duxf3 (De Iaco et al. 2017a), which will be discussed in more detail later, DPPA2 and DPPA4 (Eckersley-Maslin et al. 2019) or NELFA, acting upstream of DUX (Hu et al. 2020). However, genetic deletions of these genes individually were shown to be compatible with early embryonic development, and therefore, neither DUX nor DPPA2/4 alone seems to be responsible for inducing the totipotent state/transcription program (Chen & Zhang 2019, Chen et al. 2021). In general, most proteins identified in oocytes do not seem to be specific for these cells, which implies that the combination and stoichiometry of the various reprogramming factors rather than the presence of one unique protein is important. Indeed, the stoichiometry of reprogramming factors is vital in experiments using induced pluripotency (Buganim et al. 2013, Papp & Plath 2013). To fully understand the reason behind the relatively high reprogramming efficiency elicited by oocytes, a semi-quantitative oocyte proteome might be instructive (Israel et al. 2019a).

Remodeling

The key to successful development is the reorganization of the nucleus, accommodating different reprogramming factors and where the reprogramming factors might act upon the newly introduced genomes. Due to their large size, the oocytes and eggs provide the majority of the building blocks for the early embryonic stages. Simply put, the egg dictates the morphology of the resulting pronuclei and the uptake of the available remodeling factors. At the same time, the behavior of the sperm head, which penetrated the oocyte or egg, or the transferred nucleus, closely follows the physiological stage of the oocyte or the cytoplast stage. The main driver of the overall behavior is the maturation-promoting factor (MPF), a complex of cyclin B (gene Ccnb1) and CDK1 kinase. In the GV stage, oocytes are arrested throughout the growth phase at the dictyate stage. Therefore, they contain an intact nucleus with typical sub-nuclear bodies of low MPF activity.

When the sperm head or the somatic nucleus is introduced into either intact or enucleated GV stage oocytes, their nuclear envelopes are not disassembled, and only moderate morphological changes can be observed. The sperm head and the somatic nuclei respond to the GV cytoplasm by moderate swelling, indicating limited remodeling activity. However, as oocytes re-initiate meiosis, the MPF activity increases, the germinal vesicles disassemble, the chromosomes condense and a spindle is formed. At this phase, the GV nuclear components are released to the cytoplasm and are available to the sperm genome or an introduced somatic nucleus. Some proteins involved in the nuclear assembly, such as histones, components of the nuclear pore complex like Nup107-160 complex and ALADIN (AAAS) (Walther et al. 2003, Carvalhal et al. 2017), or NUMA1, a structural nuclear and spindle protein (Kolano et al. 2012, Kiyomitsu & Boerner 2021), might remain associated with the maternal chromosomes or in the vicinity of the maternal spindle. Although the general nuclear disassembly and reassembly principles, as we know them from somatic cells, are also applicable to oocytes, eggs and zygotes, the actual composition of the (pro)nuclei is primarily unknown. In somatic cells, the repressed chromatin typically clusters at the nuclear periphery and associates with the nuclear lamina, a prominent nuclear structural component (Reddy et al. 2008); for review, see van Steensel & Belmont 2017. Based on the available proteomic data, some of the nuclear structural components with the potential to interact with chromatin and participate in genome organization and/or gene expression, for example, lamin B1, seem to be rather stable between eggs and early embryos, while the levels of others, for example, lamin A/C, B2, emerin or LEMD3, are declining following fertilization (Israel et al. 2019a,b). Although the information about the quantities of the nuclear structural components in eggs and early embryos can be at least partially extracted from the available proteomic datasets (Gao et al. 2017, Israel et al. 2019a), this approach has its limitation with respect to the actual nuclear composition: the parental pronuclei were shown to be functionally and compositionally distinct while residing in the common cytoplasm, for example see Liu et al. 2014, Borsos et al. 2019. For this reason, the functional implication of the levels of nuclear structural proteins in the 3D nuclear organization in developing and following SCNT requires further experimental examination.

The nuclear factor CTCF has been described as one of the major players in higher order chromatin structure maintenance by localizing to TAD boundaries (Wutz et al. 2017). Contrasting results were obtained regarding the CTCF retention on mitotic chromosomes (Burke et al. 2005, Oomen et al. 2019), and it is unclear if the removal of maternal chromosomes during SCNT procedure might alter its levels. When depleted in embryos, the higher order chromatin organization is lost (Chen et al. 2019, Dequeker et al. 2022). Embryos from transgenic RNAi oocytes with a reduced CTCF were arrested in development with defects in genome activation, among others (Wan et al. 2008). This is interesting, since in somatic cells, CTCF depletion causes only a relatively mild change in the gene expression profile (Nora et al. 2017). However, the pronucleus transfer experiments performed by Wan and colleagues indicate that the arrest of knockdown CTCF embryos can be attributed to a cytoplasmic defect rather than an aberrant pronuclear architecture raising the question of how developmentally important the nuclear architecture of the parental pronuclei is (Wan et al. 2008). The described reduction of CTCF, resulting in the loss of TADs and loops (Dequeker et al. 2022), might be even beneficial for normal development from a certain perspective as CTCF was shown to represent a barrier to reprogramming by suppressing Duxf3, one of the earliest genes expressed by embryos (Olbrich et al. 2021). In the case of other factors implicated in TAD and loop establishment and maintenance, namely cohesin or WAPL, a key regulator of cohesion turnover (Wutz et al. 2017), the analysis is rather complicated. Although their deletion has been shown to affect the higher-order genome organization in the zygote (Gassler et al. 2017), their involvement in faithful chromosome segregation in oocyte meiosis (Silva et al. 2020) or embryonic mitosis (Tachibana-Konwalski et al. 2010) is limiting the use of the genetic knockout models. Nevertheless, the weak chromatin compartmentalization seems to be important for a successful development and the depletion of cohesin was shown to be beneficial for the reprogramming by promoting the early expressed zygotic genes (Zhang et al. 2020).

As evident from the description of the known reprogramming and remodeling factors, the establishment of totipotency is characterized by an extensive interplay of the transcriptional program and the higher-order chromatin organization. Next, we will describe the different stages of the female germ cell, or the cytoplasts generated thereby, and the extent of reprogramming and remodeling they can elicit in sperm or in the introduced somatic nucleus.

Reprogramming and remodeling activity in GV stage oocytes

While natural fertilization occurs at the MII stage and MII cytoplasts are almost exclusively used for SCNT, an interesting question of whether the MII stage is indeed special can be put forward: Is this stage indeed unique in terms of the reprogramming activity, i.e. the makeup of the reprogramming factors, or is it the combination of the reprogramming and remodeling activities, which expose the somatic chromatin to the egg environment and largely de novo build a nucleus, that leads to success?

Because the GV-staged cytoplasts or intact GVs have low MPF activity, as documented by the presence of a large nucleus, the transferred nucleus also remains intact, and the nuclear envelope does not disassemble (Fig. 2A). Therefore, to be able to reach and act on the somatic chromatin and to be incorporated, the oocyte material must be mostly actively imported into the somatic nucleus. When co-incubated in the same cytoplasmic environment for an extended period, only a moderate enlargement of the somatic nucleus can be observed (Fulka et al. 2009). The oocyte cannot silence the ongoing transcription in the somatic nucleus, and the exchange of nuclear components between the GV and the somatic nucleus is limited overall (Fulka et al. 2009). Essentially, the same results are also obtained when the whole GV is removed (Gao et al. 2002). This is understandable as the GV likely contains the majority of the nuclear material of the oocyte. Likewise, when the sperm fuses or is injected into intact GVs or completely enucleated GV cytoplasts, only moderate swelling of the sperm head is detected (Pyrzyńska et al. 1996), which indicates a limited import of nuclear factors. The remodeled sperm head also morphologically resembles the intact sperm head (Pyrzyńska et al. 1996). Therefore, we may assume that the remodeling and reprogramming factors must be released from the GV and made available to alter the sperm head or the somatic cell nucleus.

Figure 2
Figure 2

The effect and outcome of SCNT on different types of cytoplasts. The major driving force of the remodeling activity seems to be the MPF activity. Under its influence, the nucleus disassembles, which likely results in the availability of the structural nuclear components and specific remodeling factors (darker pink). This also influences the extent of somatic material removal (green) and exchange for the oocyte/embryonic materials.

Citation: Reproduction 165, 3; 10.1530/REP-22-0124

The procedures that help elucidate the extent of the reprogramming confined to the GV are directly injecting somatic nuclei into germinal vesicles or selective enucleation. The direct injection of the somatic nucleus has been successfully performed in Xenopus. In this case, the authors observed relatively rapid changes in gene expression driven by the exchange and activity of the oocyte-specific factors, such as the oocyte-specific linker histone B4 (Jullien et al. 2014). In mammals, however, direct injection of a somatic nucleus into GVs is technically very challenging due to the relatively small size of the GV. The problem can be partially tackled by using ‘selective enucleation’, during which the nuclear envelope, the attached chromatin and thus tightly bound chromatin factors are removed from the oocyte (Modliński, 1975). This experiment showed that the soluble GV fraction is key to modifying the transferred somatic nucleus (Fulka et al. 2019). With a prolonged incubation of the somatic nucleus in this type of a cytoplast, the somatic cell nucleus markedly enlarges. This also stimulates the exchange of some nuclear components and leads to transcriptional silencing of the transferred nucleus. For example, replacing the canonical histones H3.1/H3.2 with the histone variant H3.3 is boosted compared to completely enucleated GV cytoplasts or when intact GV oocytes are used as recipients for SCNT (Fulka et al. 2019). Although the soluble GV content is not yet well characterized, it is also essential for sperm head decondensation (Ogushi et al. 2005). Therefore, the non-chromatin/non-nuclear envelope (NC/NE) GV content seems to have a decisive role in remodeling the introduced nucleus. However, what precisely this GV fraction is composed of remains to be determined, and the extent of reprogramming elicited by the NC/NE GV fraction remains experimentally tested.

The nuclear structure, which is released to the cytoplasm during the selective enucleation, experimentally shown to be essential for remodeling of the transferred nucleus as well as for the development of embryos generated by IVF or SCNT is the NLBs (Ogushi et al. 2008). When oocytes transit from the NSN to the SN state, the transcription ceases, and the embedded chromatin detaches from the previously active nucleoli (Chouinard 1971). This might make the NLB release into the cytoplasm possible. Although NLBs are not necessary for the maturation of oocytes, they were shown to be indispensable for further embryonic development. These structures are maternally inherited, i.e. the material is not replenished after fertilization (Ogushi et al. 2008). How the NLB material might be involved in embryogenesis is still unclear, but one of its functions might be in providing a repressive compartment (Percharde et al. 2018, Xie et al. 2022), a function well-described in somatic cells (Bersaglieri & Santoro 2019).

Although the GV content seems to play a significant role in both the reprogramming and remodeling of the sperm head or the introduced somatic nucleus, it should be noted that the oocyte cytoplasm does also exhibit some activity. In 2008, Bui and colleagues performed experiments aimed at addressing this issue (Bui et al. 2008). In an elegant set of experiments, the authors showed that the cytoplasm of a GV oocyte has beneficial effects on the reprogramming of somatic cell nuclei by promoting histone deacetylation and demethylation, increasing the number of animals born after SCNT.

The above-described experiments also help us understand the different materials and structural components present in oocytes. In other words, the components of the GV are used to construct the parental pronuclei after fertilization or the (pseudo)pronucleus when the somatic cell is used. However, we still know very little about the effects of an altered stoichiometry of many oocyte components: polyspermic fertilization or the intracytoplasmic sperm injection (ICSI) of multiple sperm heads at the metaphase II stage, which will be discussed in more detail next, can lead to the formation of male pronuclei. Also, other factors are likely in abundance as the male pronuclei were shown to replicate and up to five male pronuclei undergo active demethylation (Santos et al. 2002). This indicates the excess of both structural and reprogramming components present in oocytes. Nevertheless, the kinetics and extent of the replication and demethylation in polyspermic zygotes have not been studied in detail; therefore, it cannot be ruled out that these processes proceed at a slower pace.

Reprogramming and remodeling activity in MII eggs

Natural and assisted fertilization occurs at the metaphase II stage in most mammals. Likewise, cytoplasts derived from MII eggs are almost exclusively used as recipients for SCNT (Fig. 2B, Table 1).

Table 1

Summary of efficiencies of various SCNT protocols and their modifications.

Cytoplast stage Reference Reported efficiency, donor cell (full term) Protocol modification Mode of action
GV NA NA NA NA
MII Wakayama et al. 1998 2.8% cumulus NA NA
MII Egli et al. 2009 12% embryonic stem cell NA NA
MII Kishigami et al. 2006 6.5% cumulus Trichostatin A Histone deacetylase inhibition
MII Matoba et al. 2014 8.7% Sertoli/7.6% cumulus Kdm4d mRNA injection H3K9me3 demethylation
MII Liu et al. 2016 11% Kdm4b +Kdm5b mRNA injection H3K9me2/3 + H3K4me2/3 demethylation
MII Inoue et al. 2010 14.4% Sertoli/12.7% cumulus Xist ablation ?
MII Matoba et al. 2018 23.5% Sertoli/18.7% cumulus Xist ablation + Kdm4d mRNA injection ?
MII Yang et al. 2021 6.3% cumulus Duxf3 mRNA injection ?
Zygote (metaphase) Egli et al. 2009 5% embryonic stem cell NA NA
Two cell (metaphase) Egli et al. 2009 2% embryonic stem cell NA NA
Two cell (interphase) Kang et al. 2014 4.5% embryonic stem cell NA NA

From the remodeling/reprogramming perspective, the naturally high MPF activity of the egg or the MII-derived cytoplast induces the disassembly of the nuclear envelope of the sperm head or the somatic cell nucleus, exposing the chromatin to the reprograming and remodeling factors. When compared to GV-derived cytoplasts, the egg and MII-derived cytoplasts contain additional reprogramming and remodeling factors. Although the comprehensive oocyte and egg translatome has been published only recently (Hu et al. 2022, Xiong et al. 2022), SMARCA4/BRG1 and SIN3A, both being components of chromatin remodeling complexes and accumulating during oocyte maturation, were experimentally shown to be important for post-fertilization reprogramming (Bultman et al. 2006, Egli & Eggan 2010, Jimenez et al. 2015). In somatic cells, SMARCA4/BRG1 was shown to be inactivated during mitosis by phosphorylation (Sif et al. 1998), and in eggs, SIN3A seems to be not enriched on chromosomes (Jimenez et al. 2015). It seems plausible that both SMARCA4/BRG1 and SIN3A are maintained in the cytoplast during the removal of maternal chromosomes but likely require the re-establishment of an interphase nucleus for their activity.

Under the influence of the egg cytoplasm, the fertilization is accompanied by the condensation-decondensation cycle of the sperm chromatin, which likely reflects the removal of protamines and denudation of the sperm DNA coupled with histone incorporation and condensation under the MPF influence. The histone association with the sperm DNA is necessary for the subsequent formation of the pronucleus as both depletion of H3.3 or HIRA abrogates its formation (Inoue & Zhang 2014). The transferred somatic nucleus similarly responds to the MII cytoplasmic environment by the so-called premature chromatin condensation (PCC). Unlike the sperm, the somatic cell already contains histones and other proteins associated with their DNA. Nevertheless, the somatic histones are also rapidly and extensively exchanged in the somatic chromatin following the transfer (Nashun et al. 2011). However, unlike during fertilization, where the histone variant H3.3 is the prevailing histone H3 species incorporated into the parental chromatin, a noticeable re-incorporation of the canonical somatic histone H3.1/H3.2 was observed after SCNT (Nashun et al. 2011). The pronounced incorporation of the canonical H3 histones in SCNT embryos indicates that the somatic nucleus also introduces the machinery necessary for their incorporation, possibly the replication-dependent histone chaperone complex CAF-1, for review see Grover et al. 2018. CAF-1 complex, among others, has been demonstrated to prevent the reprogramming process in somatic cells (Cheloufi et al. 2015, Ishiuchi et al. 2015). Interestingly, the H3.1/H3.2 incorporation in SCNT embryos seems to be uncoupled from replication as these variants were incorporated into pronuclei even in the presence of Aphidicolin (Nashun et al. 2011). However, the presence and incorporation of the histone H3 variants during embryogenesis is not a black-and-white issue as a tight regulation and a close interplay between all three histone H3 variants were shown to be required for a successful development (Ishiuchi et al. 2021).

At another level of epigenetic regulation, the histone PTMs are also remodeled after fertilization, and an epigenetic asymmetry between the parental pronuclei is established. While the maternal genome exhibits somatic-like features and the remodeling is less extensive, the paternal genome is generally devoid of repressive histone modifications. Some of these PTMs, including H3K9me2/3 or H3K27me3, appear only after replication in the paternal pronucleus while being present in the maternal one from the very beginning; for review, see Burton & Torres-Padilla 2014. These repressive histone modifications are also associated with the somatic chromatin, and while the somatic histones are rapidly exchanged for the oocyte ones, this exchange is not complete. Regions of high H3K9 methylation were termed reprogramming resistant regions and represent a barrier to reprogramming (Matoba et al. 2014). By introducing Kdm4d mRNA, these regions can be successfully reprogrammed, and the efficiency of SCNT increases (Matoba et al. 2014). However, the road to totipotency seems to be more complicated, as the addition of trichostatin A (TSA), a histone deacetylase inhibitor known to enhance the SCNT efficiency, in combination with Kdm4d does not further improve the SCNT efficiency when compared to TSA treatment alone (Matoba et al. 2014). From these observations, one might speculate that the egg is more equipped to add histone PTMs than to remove them gradually. However, the actual dynamics and to what extent the maternal PTMs are removed and reestablished soon after fertilization remain to be experimentally determined.

The 3D genome organization also changes with fertilization and upon the exposure of the somatic nucleus to the environment of egg cytoplasm. In contrast to the egg, even the highly compacted sperm chromatin exhibits organization into loops, TADs and compartments (Luo et al. 2020). After fertilization, a distinct chromatin organization can be observed between the maternal and paternal genomes, with the maternal one exhibiting weak segregation of compartments (Flyamer et al. 2017). Although it is unclear why the parental genomes exhibit a differential genome organization and what the implications of this observation are, this might be linked to the asymmetric epigenetic modification between the parental pronuclei. The chromatin architecture following SCNT has recently been described by Chen and colleagues (Chen et al. 2020). The authors found that the higher-order chromatin elements were rapidly removed following the nuclear transfer. This coincides with the nuclear disassembly and PCC of the somatic chromosomes induced by the high MPF activity of the recipient cytoplast. Empirically, the time during which the somatic nucleus is exposed to the mitotic egg cytoplasm seems to be essential, and both too long and too short time of exposure of the somatic chromatin to the egg cytoplasm was shown to have rather adverse effects on the development (Wakayama & Yanagimachi 2001). The typical M-phase signature was observed at early time points following transfer (Du et al. 2017). However, at a later time point, neither TADs nor the A and B compartments of SCNT embryos recapitulated the state detected during normal embryogenesis, indicating an incomplete remodeling (Chen et al. 2020). The chromatin state of the SCNT embryos was partially normalized by the injection of the H3K9me2/3 demethylase Kdm4d mRNA (Chen et al. 2020). The authors did not observe the same effect when TSA was used, although this drug has been previously shown to improve the developmental ability of SCNT embryos and has a long history in the field (Kishigami et al. 2006).

Much less is known about the interaction of the oocyte and embryonic genome with the structural elements of the nuclei. Only the lamin B1-interacting lamina-associated domains (B1-LADs) were recently mapped in oocytes and during the preimplantation development (Borsos et al. 2019). In somatic cells, lamin B- and lamin A-interacting sequences were shown to be very similar (Meuleman et al. 2013), however, whether this is also true in developing embryos and following SCNT when the levels of individual lamin proteins seem to be dynamically changing is currently unknown.

The lack of typical B1-LADs in the GV stage oocytes, which coincided with the marked chromatin condensation and association of the chromatin with the NLBs in the SN-stage oocytes, is not too surprising. The maternal B1-LADs were shown to be established de novo after fertilization and the parental-specific differences were not resolved before the eight-cell stage coinciding with the general chromatin architecture. Unfortunately, the alterations in LADs, if any, following SCNT were not tested. Whether some sequences change the positions and whether this is developmentally relevant remain unknown. Interestingly, although somatic LADs are enriched for H3K9 methylation – a repressive epigenetic histone mark (Kind et al. 2013), the B1-LAD establishment following fertilization does not seem to depend on this histone PTM as the injection of Kdm4d mRNA did not alter the pattern. However, the situation following SCNT might be different, and ideally, the somatic LADs would need to be erased and new ones established. In this respect, the occurrence of PCC might be important as it has been shown that LADs are often not conserved between two mitotic cycles (Kind et al. 2013). In contrast to somatic cells, the paternal LAD establishment was reported to be dependent on the H3K4me3 (Borsos et al. 2019). The interaction of the embryonic genome with other nuclear structures is currently unknown. However, we may presume that the persistent expression of specific somatic proteins, like the canonical histone H3 chaperones, will interfere with establishing a fully embryo-like 3D chromatin organization. Moreover, all the studies above highlight the differences between the maternal and paternal genomes. Taking this into account, should one try to mimic the embryo with the SCNT procedure, and which of the two parental states should one try to achieve?

From the structural point of view, because the preceding nuclear envelope breakdown and chromosome condensation exposed the introduced chromatin to the egg cytoplasm, where the nuclear factors are now also dispersed, it is difficult to determine, which of the egg components, nucleus vs cytoplasm, have the greatest effects on sperm/somatic chromatin in terms of reprogramming and remodeling. Nevertheless, from the results obtained from the experiments using GV stages cytoplasts, we may assume it is the nuclear components, which become released into the cytoplasm with the re-initiation of meiosis and the germinal vesicle breakdown. However, part of the factors might also associate with the egg chromatin or be organized as part of the metaphase II spindle. During SCNT, these factors might be partially replaced by the somatic cell nucleus. It has been shown that some nuclear components, such as lamin A/C or NUMA1, might be expressed from the somatic nucleus (Moreira et al. 2003). However, other experiments show that it is unlikely that the egg spindle–chromosome complex would be essential as androgenetic embryos were obtained by its removal followed by in vitro fertilization (IVF) or intracytoplasmic sperm injection (Yang et al. 2012). Moreover, after a mild depletion of the factors bound to the spindle and chromosomes, the Wakayama group achieved a better SCNT efficiency (Konno et al. 2020). Just like in the case of the NLB material, the factors associated with the egg spindle were shown not to be replenished when removed and depleted (Konno et al. 2020). Therefore, while the spindle and the chromatin are unlikely to present a structure, which binds essential remodeling and reprogramming developmental factors, the experiments by Konno and colleagues again point to the notion of stoichiometry both in the sense of protein complexes and the DNA to reprogramming factor ratios (Konno et al. 2020). Nevertheless, the question of the reprogramming factor-to-DNA ratio seems to be rather complicated and conflicting results can be found in the literature: on one hand, some authors reported that increasing the amount of the reprogramming factors present by MII cytoplast fusion is not beneficial in terms of the SCNT efficiency outcomes (Sayaka et al. 2008). On the other hand, others claimed that introducing extra cytoplasm to the cytoplasts leads to better developmental rates to the blastocyst and increased H3K9/K14 acetylation (Song et al. 2020). At the same time, the hand-made cloning, during which the egg is bisected into two halves and the half lacking the spindle is used as recipient cytoplast, has been used with success in large animals; for review, see Verma et al. 2015, Saini et al. 2018.

Although the reduced size cytoplasts are not typically used in the laboratory mouse, the hand-made cloning raises the question of whether the full content of cytoplast reprogramming and remodeling factors is indeed needed to achieve the SCNT success and whether the cytoplast impacts the transferred nucleus only in a positive manner. Actually, the opposite might be the case: One of the effects of the SCNT procedure described in the mouse is aberrant activation of Xist, a ncRNA responsible for X-chromosome inactivation in female mammals; for review, see Dossin & Heard 2022. Under normal circumstances, the paternal Xist is expressed early in development and contributes to the imprinted X-chromosome inactivation (Borensztein et al. 2017). In SCNT embryos, the Xist upregulation was observed for embryos of both sexes leading to an ectopic expression in male clones and frequent biallelic expression in female ones (Inoue et al. 2010). Interestingly, while the deletion of one Xist allele was described to have negative impact on the global transcriptome in in vivo-generated embryos, the deletion of Xist greatly enhanced the development in the SCNT experiments (Inoue et al. 2010, Matoba et al. 2018); for efficiency comparison with other SCNT modification, see Table 1. Although the mechanism by which Xist aberrant expression causes the developmental failure and by which its expression is activated following SCNT in the first place is currently unknown, one of the candidates is Kdm5c, an H3K4me2/3 demethylase as its ectopic expression activated the Xist enhancer and induce Xist expression in male cells (Samanta et al. 2022). At the same time, H3K9ac, a typical activating epigenetic mark, was reported to be increased at this locus in a DUX-dependent manner (Yang et al. 2021). The above experiments thus point to an interesting possibility that reducing the reprogramming activity of cytoplasts could actually be beneficial and it would be interesting to test, whether the Xist locus responds to the reduced amount of the reprogramming factors in an all-or-nothing fashion. At the same time, it is evident that the transferred somatic nucleus does not recapitulate faithfully the behavior of either parental genome.

Reprogramming and remodeling activity at embryonic stages

The experiments above demonstrate the incredible ability of the female germ cells to support the full-term development even when challenged by a very unusual ‘substrate’, the somatic nucleus, by providing both the building blocks and the reprogramming factors. From the perspective of totipotency, the difference between MII eggs and embryos before the genome activation, when the embryos start expressing their mRNA, should be minimal. Interestingly, enucleated zygotes were considered unsuitable recipients for nuclear transfer (Fig. 2C). Moreover, an ICSI delayed by more than 1 h for the egg activation was shown to markedly abrogate the DNA replicational licensing of the paternal genome (Yamauchi et al. 2009). These experiments indicated that the time window around the egg activation is developmentally critical for normal development and SCNT. Essentially, the same results on the critical peri-activation window were obtained when the role of NLBs was investigated (Ogushi & Saitou 2010). Therefore, these results indicate that development mostly fails once this remodeling and reprogramming window is missed. However, there might be an alternative explanation. In the case of SCNT using zygotes to generate the cytoplasts, Wakayama and colleagues removed the pronuclei, which likely contained both a portion of the structural components and the reprogramming factors (Wakayama et al. 2000). In the second case, it is known that MPF activity drops sharply with activation. The insufficient MPF activity likely led to only a partial or absent sperm head disassembly and interfered with the pronucleus formation. Therefore, these results might depend more on the methods used to generate the embryos than on the qualitative difference of remodeling and reprogramming factor content between eggs and the early embryos.

Indeed, it seems that if the factors are released from the nuclei and made available, for example by using the selective enucleation of zygotes, the cytoplasts derived from zygotes can be used as recipients for SCNT and development to term can be achieved (Greda et al. 2006). However, the extent of the reprogramming and remodeling elicited by the cytoplast depleted of chromatin factors and nuclear envelope-bound proteins is difficult to judge as only eight cell blastomere nuclei were used as nuclear donors. These are naturally both developmentally less advanced when compared to adult somatic cells, for example, cumulus cells, which are frequently used as nuclear donors in SCNT experiments, and also, their nuclei are much larger; therefore, the introduced nuclei provide a significant pool of nuclear building blocks.

However, by using the embryonic M-phase when the factors are released into the zygotic cytoplasm just like when using MII eggs to obtain cytoplasts, it is possible to achieve full-term development by SCNT using more developmentally advanced cells, such as embryonic stem cells (Egli & Eggan 2010, Liu et al. 2014). These experiments showed that the reprogramming factors are indeed sequestered in the parental pronuclei and must be released before SCNT for the procedure to be successful. Moreover, Liu and colleagues (Liu et al. 2014) showed that a higher reprogramming activity is associated with the male pronucleus by using cytoplast produced by removal of either the maternal or the paternal pronucleus. Likewise, even complementing the haploid parthenogenetic embryos by injecting sperm in the first embryonic metaphase can produce live mice (Suzuki et al. 2016). This indicates that factors responsible for establishing totipotency and a successful development are still present during both the first and the second embryonic cell cycle, albeit at lower levels. Although these results refute the importance of the critical peri-fertilization window as mentioned before, the highest reprogramming and remodeling activity does indeed seem to be present around the time of fertilization.

In agreement with this notion, the genes of the Dux cluster are expressed around this time and have thus attracted a substantial attention. The cluster contains two main transcripts: the full-length Dux (Duxf3) and a truncated version Gm4981 (Duxf4) expressed mainly in oogenesis (De Iaco et al. 2017a ). In this work, the authors proposed that DUX could act as a pioneer transcription factors (De Iaco et al. 2017b ). These generally have the ability to target DNA on the surface of nucleosomes; for review, see (Mayran & Drouin 2018, Zaret 2020). In line with its proposed function, its human homolog DUX4 was shown to contain multiple nuclear localization signals conferring a strong nuclear accumulation (Mitsuhashi et al. 2018). It seems to participate not only in the regulation of endogenous genes, such as Zscan4, but also retroviral elements ERVL family repeats and associated genes (De Iaco et al. 2017a , Hendrickson et al. 2017). In the context of reprogramming, the ectopic expression of Dux was shown to enhance the efficiency of SCNT by normalizing the SCNT embryo expression program (Yang et al. 2020, Huang et al. 2021). Although its expression was proposed to be essential for establishing the totipotent state, its ectopic introduction did not majorly affect the SCNT efficiency (Yang et al. 2020) and the knockout experiments do not support its essentiality; the genetic ablation of both Dux and Gm4981 causes only minor defects and is compatible with life (Chen & Zhang 2019). On the other hand, the overexpression of DUX in somatic cells is known to be detrimental (Geng et al. 2012). Therefore, the timely shutdown of Dux expression during embryogenesis might be more important. Indeed, embryos, which were unable to inactivate its expression, were unable to exit the two-cell stage (Xie et al. 2022). Interestingly, the Dux expression shutdown seems to be achieved by the association of this gene cluster with embryonic nucleoli and its component, nucleolin (Percharde et al. 2018, Xie et al. 2022). These experiments thus provide a tentative explanation for the reported essentiality of NPBs during embryogenesis (Ogushi et al. 2008).

Now classic work by Tarkowski (Tarkowski 1959) or Tsunoda and McLaren (Tsunoda & McLaren 1983) indicated that totipotency becomes lost after the two-cell embryonic stage and although the reprogramming factors seem to be mostly confined to nuclei at interphase, the reprogramming ability of the two-cell interphase cytoplast has also been experimentally tested (Tsunoda et al. 1987, Kang et al. 2014). In a study by Tsunoda and colleagues, full-term development was achieved by reconstructing the embryos from two-cell cytoplasts and eight-cell nuclei (Tsunoda et al. 1987). Only partial reprogramming capacity of two-cell interphase cytoplasts was reported when embryonic stem cells were used as donors and the efficiency decreased further with the use of fetal fibroblast nuclei (Kang et al. 2014). In this setup, we may presume that most of the nuclear structural components were removed upon enucleation. Although it is difficult to make a conclusion, some structural nuclear components, such as lamin B, as well as the remodeling factor SMARCA4/BRG1, seem to be replenished and the overall nuclear morphology at 12 h post-SCNT does not seem to differ grossly from controls (Kang et al. 2014). However, the detailed analysis of nuclei as well as other parameters, such as expression profile, of these SCNT embryos is unknown. Nevertheless, these experiments indicate the gradual loss of the reprogramming ability as the development advances.

Conclusions and future perspectives

Although we now have the access to methods such as Hi-C and we are beginning to understand the bases of nuclear remodeling and reprogramming changes that occur during the transit from oocyte to the embryo, and even following the SCNT, we are far from understanding the impact of different protocols, modulations of the genome and nuclear architecture and patterns of remodeling and reprogramming, which deviate from the observed norm. Linking the data from the fine genome architecture mapping studies with the experiments aimed at full-term development, genetic models and proteomic analyses of oocytes and early embryos seem vital in searching for a more efficient SCNT protocol and understanding the flexible nature of mammalian development.

Declaration of interest

The authors declare no conflict of interest.

Funding

HF is supported by The Czech Science Foundation (GACR 21-42225L), JFJr is supported by NAZV (QK1910156), PL and MC are supported by the project Drynet, under the Marie Skłodowska-Curie grant (agreements No. 734434) and ‘DEMETRA’ (MIUR) Department of Excellence 2018–2022.

Author contribution statement

HF, PL, MC, AS and JF Jr. jointly wrote and prepared the manuscript.

Acknowledgement

The authors would like to dedicate this article to the memory of Robert M Moor, FRS (1937–2021), whose work significantly expanded their knowledge about mammalian oocytes and zygotes.

References

  • Bersaglieri C & Santoro R 2019 Genome Organization in and around the Nucleolus. Cells 8 579. (https://doi.org/10.3390/cells8060579)

  • Bizhanova A & Kaufman PD 2021 Close to the edge: heterochromatin at the nucleolar and nuclear peripheries. Biochimica et Biophysica Acta. Gene Regulatory Mechanisms 1864 194666. (https://doi.org/10.1016/j.bbagrm.2020.194666)

    • Search Google Scholar
    • Export Citation
  • Borensztein M, Syx L, Ancelin K, Diabangouaya P, Picard C, Liu T, Liang JB, Vassilev I, Galupa R & Servant N et al.2017 Xist-dependent imprinted X inactivation and the early developmental consequences of its failure. Nature Structural and Molecular Biology 24 226233. (https://doi.org/10.1038/nsmb.3365)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Borsos M, Perricone SM, Schauer T, Pontabry J, de Luca KL, de Vries SS, Ruiz-Morales ER, Torres-Padilla ME & Kind J 2019 Genome-lamina interactions are established de novo in the early mouse embryo. Nature 569 729733. (https://doi.org/10.1038/s41586-019-1233-0)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bouniol-Baly C, Hamraoui L, Guibert J, Beaujean N, Szöllösi MS & Debey P 1999 Differential transcriptional activity associated with chromatin configuration in fully grown mouse germinal vesicle oocytes. Biology of Reproduction 60 580587. (https://doi.org/10.1095/biolreprod60.3.580)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Buganim Y, Faddah DA & Jaenisch R 2013 Mechanisms and models of somatic cell reprogramming. Nature Reviews. Genetics 14 427439. (https://doi.org/10.1038/nrg3473)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bui HT, Wakayama S, Kishigami S, Kim JH, Van Thuan N & Wakayama T 2008 The cytoplasm of mouse germinal vesicle stage oocytes can enhance somatic cell nuclear reprogramming. Development (Cambridge, England) 135 39353945. (https://doi.org/10.1242/dev.023747)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bultman SJ, Gebuhr TC, Pan H, Svoboda P, Schultz RM & Magnuson T 2006 Maternal BRG1 regulates zygotic genome activation in the mouse. Genes and Development 20 17441754. (https://doi.org/10.1101/gad.1435106)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Burke LJ, Zhang R, Bartkuhn M, Tiwari VK, Tavoosidana G, Kurukuti S, Weth C, Leers J, Galjart N & Ohlsson R et al.2005 CTCF binding and higher order chromatin structure of the H19 locus are maintained in mitotic chromatin. EMBO Journal 24 32913300. (https://doi.org/10.1038/sj.emboj.7600793)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Burton A & Torres-Padilla ME 2014 Chromatin dynamics in the regulation of cell fate allocation during early embryogenesis. Nature Reviews. Molecular Cell Biology 15 723734. (https://doi.org/10.1038/nrm3885)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Carvalhal S, Stevense M, Koehler K, Naumann R, Huebner A, Jessberger R & Griffis ER 2017 ALADIN is required for the production of fertile mouse oocytes. Molecular Biology of the Cell 28 24702478. (https://doi.org/10.1091/mbc.E16-03-0158)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Chagin VO, Stear JH & Cardoso MC 2010 Organization of DNA replication. Cold Spring Harbor Perspectives in Biology 2 a000737. (https://doi.org/10.1101/cshperspect.a000737)

    • Search Google Scholar
    • Export Citation
  • Cheloufi S, Elling U, Hopfgartner B, Jung YL, Murn J, Ninova M, Hubmann M, Badeaux AI, Ang CE & Tenen D et al.2015 The histone chaperone CAF-1 safeguards somatic cell identity. Nature 528 218224. (https://doi.org/10.1038/nature15749)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Chen M, Zhu Q, Li C, Kou X, Zhao Y, Li Y, Xu R, Yang L, Yang L & Gu L et al.2020 Chromatin architecture reorganization in murine somatic cell nuclear transfer embryos. Nature Communications 11 1813. (https://doi.org/10.1038/s41467-020-15607-z)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Chen X, Ke Y, Wu K, Zhao H, Sun Y, Gao L, Liu Z, Zhang J, Tao W & Hou Z et al.2019 Key role for CTCF in establishing chromatin structure in human embryos. Nature 576 306310. (https://doi.org/10.1038/s41586-019-1812-0)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Chen Z, Xie Z & Zhang Y 2021 DPPA2 and DPPA4 are dispensable for mouse zygotic genome activation and pre-implantation development. Development (Cambridge, England) 148 dev200178. (https://doi.org/10.1242/dev.200178)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Chen Z & Zhang Y 2019 Loss of DUX causes minor defects in zygotic genome activation and is compatible with mouse development. Nature Genetics 51 947951. (https://doi.org/10.1038/s41588-019-0418-7)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Chouinard LA 1971 A light- and electron-microscope study of the nucleolus during growth of the oocyte in the prepubertal mouse. Journal of Cell Science 9 637663. (https://doi.org/10.1242/jcs.9.3.637)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Conti M & Franciosi F 2018 Acquisition of oocyte competence to develop as an embryo: integrated nuclear and cytoplasmic events. Human Reproduction Update 24 245266. (https://doi.org/10.1093/humupd/dmx040)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Dahl JA, Jung I, Aanes H, Greggains GD, Manaf A, Lerdrup M, Li G, Kuan S, Li B & Lee AY et al.2016 Broad histone H3K4me3 domains in mouse oocytes modulate maternal-to-zygotic transition. Nature 537 548552. (https://doi.org/10.1038/nature19360)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • De Iaco A, Planet E, Coluccio A, Verp S, Duc J & Trono D 2017 aDUX-family transcription factors regulate zygotic genome activation in placental mammals. Nature Genetics 49 941945. (https://doi.org/10.1038/ng.3858)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Dequeker BJH, Scherr MJ, Brandão HB, Gassler J, Powell S, Gaspar I, Flyamer IM, Lalic A, Tang W & Stocsits R et al.2022 MCM complexes are barriers that restrict cohesin-mediated loop extrusion. Nature 606 197203. (https://doi.org/10.1038/s41586-022-04730-0)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Dossin F & Heard E 2022 The molecular and nuclear dynamics of X-chromosome inactivation. Cold Spring Harbor Perspectives in Biology 14 a040196. (https://doi.org/10.1101/cshperspect.a040196)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Du Z, Zheng H, Huang B, Ma R, Wu J, Zhang X, He J, Xiang Y, Wang Q & Li Y et al.2017 Allelic reprogramming of 3D chromatin architecture during early mammalian development. Nature 547 232235. (https://doi.org/10.1038/nature23263)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Eckersley-Maslin M, Alda-Catalinas C, Blotenburg M, Kreibich E, Krueger C & Reik W 2019 Dppa2 and Dppa4 directly regulate the Dux-driven zygotic transcriptional program. Genes and Development 33 194208. (https://doi.org/10.1101/gad.321174.118)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Egli D & Eggan K 2010 Recipient cell nuclear factors are required for reprogramming by nuclear transfer. Development (Cambridge, England) 137 19531963. (https://doi.org/10.1242/dev.046151)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Egli D, Sandler VM, Shinohara ML, Cantor H & Eggan K 2009 Reprogramming after chromosome transfer into mouse blastomeres. Current Biology 19 14031409. (https://doi.org/10.1016/j.cub.2009.06.065)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Flyamer IM, Gassler J, Imakaev M, Brandão HB, Ulianov SV, Abdennur N, Razin SV, Mirny LA & Tachibana-Konwalski K 2017 Single-nucleus Hi-C reveals unique chromatin reorganization at oocyte-to-zygote transition. Nature 544 110114. (https://doi.org/10.1038/nature21711)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Fortin JP & Hansen KD 2015 Reconstructing A/B compartments as revealed by Hi-C using long-range correlations in epigenetic data. Genome Biology 16 180. (https://doi.org/10.1186/s13059-015-0741-y)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Fu X, Wu X, Djekidel MN & Zhang Y 2019 Myc and Dnmt1 impede the pluripotent to totipotent state transition in embryonic stem cells. Nature Cell Biology 21 835844. (https://doi.org/10.1038/s41556-019-0343-0)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Fulka H, Novakova Z, Mosko T & Fulka J 2009 The inability of fully grown germinal vesicle stage oocyte cytoplasm to transcriptionally silence transferred transcribing nuclei. Histochemistry and Cell Biology 132 457468. (https://doi.org/10.1007/s00418-009-0625-x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Fulka H, Ogura A, Loi P & Fulka J Jr 2019 Dissecting the role of the germinal vesicle nuclear envelope and soluble content in the process of somatic cell remodelling and reprogramming. Journal of Reproduction and Development 65 433441. (https://doi.org/10.1262/jrd.2019-017)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Gao S, Gasparrini B, McGarry M, Ferrier T, Fletcher J, Harkness L, De Sousa P & Wilmut I 2002 Germinal vesicle material is essential for nucleus remodeling after nuclear transfer. Biology of Reproduction 67 928934. (https://doi.org/10.1095/biolreprod.102.004606)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Gao Y, Liu X, Tang B, Li C, Kou Z, Li L, Liu W, Wu Y, Kou X & Li J et al.2017 Protein expression landscape of mouse embryos during pre-implantation development. Cell Reports 21 39573969. (https://doi.org/10.1016/j.celrep.2017.11.111)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Gassler J, Brandão HB, Imakaev M, Flyamer IM, Ladstätter S, Bickmore WA, Peters JM, Mirny LA & Tachibana K 2017 A mechanism of cohesin-dependent loop extrusion organizes zygotic genome architecture. EMBO Journal 36 36003618. (https://doi.org/10.15252/embj.201798083)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Geng LN, Yao Z, Snider L, Fong AP, Cech JN, Young JM, van der Maarel SM, Ruzzo WL, Gentleman RC & Tawil R et al.2012 DUX4 activates germline genes, retroelements, and immune mediators: implications for facioscapulohumeral dystrophy. Developmental Cell 22 3851. (https://doi.org/10.1016/j.devcel.2011.11.013)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Greda P, Karasiewicz J & Modlinski JA 2006 Mouse zygotes as recipients in embryo cloning. Reproduction (Cambridge, England) 132 741748. (https://doi.org/10.1530/rep.1.01204)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Grover P, Asa JS & Campos EI 2018 H3-H4 Histone chaperone pathways. Annual Review of Genetics 52 109130. (https://doi.org/10.1146/annurev-genet-120417-031547)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Gurdon JB & Melton DA 2008 Nuclear reprogramming in cells. Science (New York, NY) 322 18111815. (https://doi.org/10.1126/science.1160810)

  • Hake SB & Allis CD 2006 Histone H3 variants and their potential role in indexing mammalian genomes: the “H3 barcode hypothesis”. Proceedings of the National Academy of Sciences of the United States of America 103 64286435. (https://doi.org/10.1073/pnas.0600803103)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Hansen AS, Cattoglio C, Darzacq X & Tjian R 2018 Recent evidence that TADs and chromatin loops are dynamic structures. Nucleus (Austin, Tex.) 9 2032. (https://doi.org/10.1080/19491034.2017.1389365)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Heinz KS, Casas-Delucchi CS, Török T, Cmarko D, Rapp A, Raska I & Cardoso MC 2018 Peripheral re-localization of constitutive heterochromatin advances its replication timing and impairs maintenance of silencing marks. Nucleic Acids Research 46 61126128. (https://doi.org/10.1093/nar/gky368)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Hendrickson PG, Doráis JA, Grow EJ, Whiddon JL, Lim JW, Wike CL, Weaver BD, Pflueger C, Emery BR & Wilcox AL et al.2017 Conserved roles of mouse DUX and human DUX4 in activating cleavage-stage genes and MERVL/HERVL retrotransposons. Nature Genetics 49 925934. (https://doi.org/10.1038/ng.3844)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Holwerda S & De Laat W 2012 Chromatin loops, gene positioning, and gene expression. Frontiers in Genetics 3 217. (https://doi.org/10.3389/fgene.2012.00217)

  • Hörmanseder E, Simeone A, Allen GE, Bradshaw CR, Figlmüller M, Gurdon J & Jullien J 2017 H3K4 Methylation-dependent memory of somatic cell identity inhibits reprogramming and development of nuclear transfer embryos. Cell Stem Cell 21 135143.e6. (https://doi.org/10.1016/j.stem.2017.03.003)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Hu W, Zeng H, Shi Y, Zhou C, Huang J, Jia L, Xu S, Feng X, Zeng Y & Xiong T et al.2022 Single-cell transcriptome and translatome dual-omics reveals potential mechanisms of human oocyte maturation. Nature Communications 13 5114. (https://doi.org/10.1038/s41467-022-32791-2)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Hu Z, Tan DEK, Chia G, Tan H, Leong HF, Chen BJ, Lau MS, Tan KYS, Bi X & Yang D et al.2020 Maternal factor NELFA drives a 2C-like state in mouse embryonic stem cells. Nature Cell Biology 22 175186. (https://doi.org/10.1038/s41556-019-0453-8)

    • Search Google Scholar
    • Export Citation
  • Huang X, Hu X, Jiang Q, Cao Q, Wu Y & Lei L 2021 Functional study of distinct domains of Dux in improving mouse SCNT embryonic development†. Biology of Reproduction 105 10891103. (https://doi.org/10.1093/biolre/ioab141)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Inoue A, Nakajima R, Nagata M & Aoki F 2008 Contribution of the oocyte nucleus and cytoplasm to the determination of meiotic and developmental competence in mice. Human Reproduction 23 13771384. (https://doi.org/10.1093/humrep/den096)

    • Search Google Scholar
    • Export Citation
  • Inoue A & Zhang Y 2014 Nucleosome assembly is required for nuclear pore complex assembly in mouse zygotes. Nature Structural and Molecular Biology 21 609616. (https://doi.org/10.1038/nsmb.2839)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Inoue K, Kohda T, Sugimoto M, Sado T, Ogonuki N, Matoba S, Shiura H, Ikeda R, Mochida K & Fujii T et al.2010 Impeding Xist expression from the active X chromosome improves mouse somatic cell nuclear transfer. Science (New York, NY) 330 496499. (https://doi.org/10.1126/science.1194174)

    • Search Google Scholar
    • Export Citation
  • Ishiuchi T, Abe S, Inoue K, Yeung WKA, Miki Y, Ogura A & Sasaki H 2021 Reprogramming of the histone H3.3 landscape in the early mouse embryo. Nature Structural and Molecular Biology 28 3849. (https://doi.org/10.1038/s41594-020-00521-1)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Ishiuchi T, Enriquez-Gasca R, Mizutani E, Bošković A, Ziegler-Birling C, Rodriguez-Terrones D, Wakayama T, Vaquerizas JM & Torres-Padilla ME 2015 Early embryonic-like cells are induced by downregulating replication-dependent chromatin assembly. Nature Structural and Molecular Biology 22 662671. (https://doi.org/10.1038/nsmb.3066)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Israel S, Casser E, Drexler HCA, Fuellen G & Boiani M 2019b A framework for TRIM21-mediated protein depletion in early mouse embryos: recapitulation of Tead4 null phenotype over three days. BMC Genomics 20 755. (https://doi.org/10.1186/s12864-019-6106-2)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Israel S, Ernst M, Psathaki OE, Drexler HCA, Casser E, Suzuki Y, Makalowski W, Boiani M, Fuellen G & Taher L 2019a An integrated genome-wide multi-omics analysis of gene expression dynamics in the preimplantation mouse embryo. Scientific Reports 9 13356. (https://doi.org/10.1038/s41598-019-49817-3)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Jimenez R, Melo EO, Davydenko O, Ma J, Mainigi M, Franke V & Schultz RM 2015 Maternal SIN3A regulates reprogramming of gene expression during mouse preimplantation development. Biology of Reproduction 93 89. (https://doi.org/10.1095/biolreprod.115.133504)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Jullien J, Miyamoto K, Pasque V, Allen GE, Bradshaw CR, Garrett NJ, Halley-Stott RP, Kimura H, Ohsumi K & Gurdon JB 2014 Hierarchical molecular events driven by oocyte-specific factors lead to rapid and extensive reprogramming. Molecular Cell 55 524536. (https://doi.org/10.1016/j.molcel.2014.06.024)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kang E, Wu G, Ma H, Li Y, Tippner-Hedges R, Tachibana M, Sparman M, Wolf DP, Schöler HR & Mitalipov S 2014 Nuclear reprogramming by interphase cytoplasm of two-cell mouse embryos. Nature 509 101104. (https://doi.org/10.1038/nature13134)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kind J, Pagie L, Ortabozkoyun H, Boyle S, de Vries SS, Janssen H, Amendola M, Nolen LD, Bickmore WA & van Steensel B 2013 Single-cell dynamics of genome-nuclear lamina interactions. Cell 153 178192. (https://doi.org/10.1016/j.cell.2013.02.028)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kishigami S, Mizutani E, Ohta H, Hikichi T, Thuan NV, Wakayama S, Bui HT & Wakayama T 2006 Significant improvement of mouse cloning technique by treatment with trichostatin A after somatic nuclear transfer. Biochemical and Biophysical Research Communications 340 183189. (https://doi.org/10.1016/j.bbrc.2005.11.164)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kiyomitsu T & Boerner S 2021 The nuclear mitotic apparatus (NuMA) protein: a key player for nuclear formation, spindle assembly, and spindle positioning. Frontiers in Cell and Developmental Biology 9 653801. (https://doi.org/10.3389/fcell.2021.653801)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kolano A, Brunet S, Silk AD, Cleveland DW & Verlhac MH 2012 Error-prone mammalian female meiosis from silencing the spindle assembly checkpoint without normal interkinetochore tension. Proceedings of the National Academy of Sciences of the United States of America 109 E1858E1867. (https://doi.org/10.1073/pnas.1204686109)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Konno S, Wakayama S, Ito D, Kazama K, Hirose N, Ooga M & Wakayama T 2020 Removal of remodeling/reprogramming factors from oocytes and the impact on the full-term development of cloned embryos. Development 147. (https://doi.org/10.1242/dev.190777)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Krawczyk K, Kosyl E, Częścik-Łysyszyn K, Wyszomirski T & Maleszewski M 2021 Developmental capacity is unevenly distributed among single blastomeres of 2-cell and 4-cell stage mouse embryos. Scientific Reports 11 21422. (https://doi.org/10.1038/s41598-021-00834-1)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kunitomi A, Yuasa S, Sugiyama F, Saito Y, Seki T, Kusumoto D, Kashimura S, Takei M, Tohyama S & Hashimoto H et al.2016 H1foo has a pivotal role in qualifying induced pluripotent stem cells. Stem Cell Reports 6 825833. (https://doi.org/10.1016/j.stemcr.2016.04.015)

    • Search Google Scholar
    • Export Citation
  • Levi M, Ghetler Y, Shulman A & Shalgi R 2013 Morphological and molecular markers are correlated with maturation-competence of human oocytes. Human Reproduction 28 24822489. (https://doi.org/10.1093/humrep/det261)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Liu W, Liu X, Wang C, Gao Y, Gao R, Kou X, Zhao Y, Li J, Wu Y & Xiu W et al.2016 Identification of key factors conquering developmental arrest of somatic cell cloned embryos by combining embryo biopsy and single-cell sequencing. Cell Discovery 2 16010. (https://doi.org/10.1038/celldisc.2016.10)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Liu W, Yin J, Kou X, Jiang Y, Gao H, Zhao Y, Huang B, He W, Wang H & Han Z et al.2014 Asymmetric reprogramming capacity of parental pronuclei in mouse zygotes. Cell Reports 6 10081016. (https://doi.org/10.1016/j.celrep.2014.02.018)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Luo Z, Wang X, Jiang H, Wang R, Chen J, Chen Y, Xu Q, Cao J, Gong X & Wu J et al.2020 Reorganized 3D genome structures support transcriptional regulation in mouse spermatogenesis. iScience 23 101034. (https://doi.org/10.1016/j.isci.2020.101034)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Maemura M, Taketsuru H, Nakajima Y, Shao R, Kakihara A, Nogami J, Ohkawa Y & Tsukada YI 2021 Totipotency of mouse zygotes extends to single blastomeres of embryos at the four-cell stage. Scientific Reports 11 11167. (https://doi.org/10.1038/s41598-021-90653-1)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Matoba S, Liu Y, Lu F, Iwabuchi KA, Shen L, Inoue A & Zhang Y 2014 Embryonic development following somatic cell nuclear transfer impeded by persisting histone methylation. Cell 159 884895. (https://doi.org/10.1016/j.cell.2014.09.055)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Matoba S, Wang H, Jiang L, Lu F, Iwabuchi KA, Wu X, Inoue K, Yang L, Press W & Lee JT et al.2018 Loss of H3K27me3 imprinting in somatic cell nuclear transfer embryos disrupts post-implantation development. Cell Stem Cell 23 343354.e5. (https://doi.org/10.1016/j.stem.2018.06.008)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Mayran A & Drouin J 2018 Pioneer transcription factors shape the epigenetic landscape. Journal of Biological Chemistry 293 1379513804. (https://doi.org/10.1074/jbc.R117.001232)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Meuleman W, Peric-Hupkes D, Kind J, Beaudry J-B, Pagie L, Kellis M, Reinders M, Wessels L & van Steensel B 2013 Constitutive nuclear lamina–genome interactions are highly conserved and associated with A/T-rich sequence. Genome Research 23 270280. (https://doi.org/10.1101/gr.141028.112)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Mitsuhashi H, Ishimaru S, Homma S, Yu B, Honma Y, Beermann ML & Miller JB 2018 Functional domains of the FSHD-associated DUX4 protein. Biology Open 7 bio033977. (https://doi.org/10.1242/bio.033977)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Modliński JA 1975 Haploid mouse embryos obtained by microsurgical removal of one pronucleus. Journal of Embryology and Experimental Morphology 33 897905. (https://doi.org/10.1242/dev.33.4.897)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Moore GPM & Lintern-Moore S 1974 A correlation between growth and rna synthesis in the mouse oocyte. Journal of Reproduction and Fertility 39 163166. (https://doi.org/10.1530/jrf.0.0390163)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Moreira PN, Robl JM & Collas P 2003 Architectural defects in pronuclei of mouse nuclear transplant embryos. Journal of Cell Science 116 37133720. (https://doi.org/10.1242/jcs.00692)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Nashun B, Akiyama T, Suzuki MG & Aoki F 2011 Dramatic replacement of histone variants during genome remodeling in nuclear-transferred embryos. Epigenetics 6 14891497. (https://doi.org/10.4161/epi.6.12.18206)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Nashun B, Hill PWS, Smallwood SA, Dharmalingam G, Amouroux R, Clark SJ, Sharma V, Ndjetehe E, Pelczar P & Festenstein RJ et al.2015 Continuous histone replacement by Hira is essential for normal transcriptional regulation and de novo DNA methylation during mouse oogenesis. Molecular Cell 60 611625. (https://doi.org/10.1016/j.molcel.2015.10.010)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Naumova N, Imakaev M, Fudenberg G, Zhan Y, Lajoie BR, Mirny LA & Dekker J 2013 Organization of the mitotic chromosome. Science (New York, NY) 342 948953. (https://doi.org/10.1126/science.1236083)

    • Search Google Scholar
    • Export Citation
  • Nora EP, Goloborodko A, Valton AL, Gibcus JH, Uebersohn A, Abdennur N, Dekker J, Mirny LA & Bruneau BG 2017 Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization. Cell 169 930944.e22. (https://doi.org/10.1016/j.cell.2017.05.004)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Ogushi S, Fulka J & Miyano T 2005 Germinal vesicle materials are requisite for male pronucleus formation but not for change in the activities of CDK1 and MAP kinase during maturation and fertilization of pig oocytes. Developmental Biology 286 287298. (https://doi.org/10.1016/j.ydbio.2005.08.002)

    • Search Google Scholar
    • Export Citation
  • Ogushi S, Palmieri C, Fulka H, Saitou M, Miyano T & Fulka J 2008 The maternal nucleolus is essential for early embryonic development in mammals. Science (New York, NY) 319 613616. (https://doi.org/10.1126/science.1151276)

    • Search Google Scholar
    • Export Citation
  • Ogushi S & Saitou M 2010 The nucleolus in the mouse oocyte is required for the early step of both female and male pronucleus organization. Journal of Reproduction and Development 56 495501. (https://doi.org/10.1262/jrd.09-184h)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Olbrich T, Vega-Sendino M, Tillo D, Wu W, Zolnerowich N, Pavani R, Tran AD, Domingo CN, Franco M & Markiewicz-Potoczny M et al.2021 CTCF is a barrier for 2C-like reprogramming. Nature Communications 12 4856. (https://doi.org/10.1038/s41467-021-25072-x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Oomen ME, Hansen AS, Liu Y, Darzacq X & Dekker J 2019 CTCF sites display cell cycle–dependent dynamics in factor binding and nucleosome positioning. Genome Research 29 236249. (https://doi.org/10.1101/gr.241547.118)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Papp B & Plath K 2013 Epigenetics of reprogramming to induced pluripotency. Cell 152 13241343. (https://doi.org/10.1016/j.cell.2013.02.043)

  • Percharde M, Lin CJ, Yin Y, Guan J, Peixoto GA, Bulut-Karslioglu A, Biechele S, Huang B, Shen X & Ramalho-Santos M 2018 A LINE1-Nucleolin partnership regulates early development and ESC identity. Cell 174 391405.e19. (https://doi.org/10.1016/j.cell.2018.05.043)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Pope BD, Ryba T, Dileep V, Yue F, Wu W, Denas O, Vera DL, Wang Y, Hansen RS & Canfield TK et al.2014 Topologically associating domains are stable units of replication-timing regulation. Nature 515 402405. (https://doi.org/10.1038/nature13986)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Pyrzyńska B, Maleszewski M & Maluchnik D 1996 Mouse oocytes penetrated by sperm at GV or GVBD stage lose the ability to fuse with additional spermatozoa. Zygote (Cambridge, England) 4 123128. (https://doi.org/10.1017/s0967199400002999)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Reddy KL, Zullo JM, Bertolino E & Singh H 2008 Transcriptional repression mediated by repositioning of genes to the nuclear lamina. Nature 452 243247. (https://doi.org/10.1038/nature06727)

    • Search Google Scholar
    • Export Citation
  • Saini M, Selokar NL, Palta P, Chauhan MS, Manik RS & Singla SK 2018 An update: reproductive handmade cloning of water buffalo (Bubalus bubalis). Animal Reproduction Science 197 19. (https://doi.org/10.1016/j.anireprosci.2018.08.003)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Samanta MK, Gayen S, Harris C, Maclary E, Murata-Nakamura Y, Malcore RM, Porter RS, Garay PM, Vallianatos CN & Samollow PB et al.2022 Activation of Xist by an evolutionarily conserved function of KDM5C demethylase. Nature Communications 13 2602. (https://doi.org/10.1038/s41467-022-30352-1)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Santos F, Hendrich B, Reik W & Dean W 2002 Dynamic reprogramming of DNA methylation in the early mouse embryo. Developmental Biology 241 172182. (https://doi.org/10.1006/dbio.2001.0501)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Sayaka W, Satoshi K, Van Thuan N, Hiroshi O, Takafusa H, Eiji M, Thuy BH, Masashi M & Teruhiko W 2008 Effect of volume of oocyte cytoplasm on embryo development after parthenogenetic activation, intracytoplasmic sperm injection, or somatic cell nuclear transfer. Zygote (Cambridge, England) 16 211222. (https://doi.org/10.1017/S0967199408004620)

    • Search Google Scholar
    • Export Citation
  • Shinagawa T, Takagi T, Tsukamoto D, Tomaru C, Huynh LM, Sivaraman P, Kumarevel T, Inoue K, Nakato R & Katou Y et al.2014 Histone variants enriched in oocytes enhance reprogramming to induced pluripotent stem cells. Cell Stem Cell 14 217227. (https://doi.org/10.1016/j.stem.2013.12.015)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Sif S, Stukenberg PT, Kirschner MW & Kingston RE 1998 Mitotic inactivation of a human SWI/SNF chromatin remodeling complex. Genes and Development 12 28422851. (https://doi.org/10.1101/gad.12.18.2842)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Silva MCC, Powell S, Ladstätter S, Gassler J, Stocsits R, Tedeschi A, Peters JM & Tachibana K 2020 Wapl releases Scc1-cohesin and regulates chromosome structure and segregation in mouse oocytes. Journal of Cell Biology 219 e201906100. (https://doi.org/10.1083/jcb.201906100)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Song SH, Oh SH, Xu L, Lee KL, Hwang JY, Joo MD & Kong IK 2020 Effect of additional cytoplasm of cloned embryo on in vitro developmental competence and reprogramming efficiency in mice. Cellular Reprogramming 22 236243. (https://doi.org/10.1089/cell.2020.0022)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Suzuki T, Asami M, Hoffmann M, Lu X, Gužvić M, Klein CA & Perry ACF 2016 Mice produced by mitotic reprogramming of sperm injected into haploid parthenogenotes. Nature Communications 7 12676. (https://doi.org/10.1038/ncomms12676)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Szabo Q, Bantignies F & Cavalli G 2019 Principles of genome folding into topologically associating domains. Science Advances 5 eaaw1668. (https://doi.org/10.1126/sciadv.aaw1668)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Tachibana-Konwalski K, Godwin J, van der Weyden L, Champion L, Kudo NR, Adams DJ & Nasmyth K 2010 Rec8-containing cohesin maintains bivalents without turnover during the growing phase of mouse oocytes. Genes and Development 24 25052516. (https://doi.org/10.1101/gad.605910)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Takahashi K & Yamanaka S 2006 Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126 663676. (https://doi.org/10.1016/j.cell.2006.07.024)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Tanaka M, Hennebold JD, Macfarlane J & Adashi EY 2001 A mammalian oocyte-specific linker histone gene H1oo: homology with the genes for the oocyte-specific cleavage stage histone (cs-H1) of sea urchin and the B4/H1M histone of the frog. Development (Cambridge, England) 128 655664. (https://doi.org/10.1242/dev.128.5.655)

    • Search Google Scholar
    • Export Citation
  • Tarkowski AK 1959 Experiments on the development of isolated blastomers of mouse eggs. Nature 184 12861287. (https://doi.org/10.1038/1841286a0)

  • Tsunoda Y & McLaren A 1983 Effect of various procedures on the viability of mouse embryos containing half the normal number of blastomeres. Journal of Reproduction and Fertility 69 315322. (https://doi.org/10.1530/jrf.0.0690315)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Tsunoda Y, Yasui T, Shioda Y, Nakamura K, Uchida T & Sugie T 1987 Full-term development of mouse blastomere nuclei transplanted into enucleated two-cell embryos. Journal of Experimental Zoology 242 147151. (https://doi.org/10.1002/jez.1402420205)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • van Steensel B & Belmont AS 2017 Lamina-associated domains: links with chromosome architecture, heterochromatin and gene repression. Cell 169 780791. (https://doi.org/10.1016/j.cell.2017.04.022)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Verma G, Arora JS, Sethi RS, Mukhopadhyay CS & Verma R 2015 Handmade cloning: recent advances, potential and pitfalls. Journal of Animal Science and Biotechnology 6 43. (https://doi.org/10.1186/s40104-015-0043-y)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wakayama T, Perry AC, Zuccotti M, Johnson KR & Yanagimachi R 1998 Full-term development of mice from enucleated oocytes injected with cumulus cell nuclei. Nature 394 369374. (https://doi.org/10.1038/28615)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wakayama T, Tateno H, Mombaerts P & Yanagimachi R 2000 Nuclear transfer into mouse zygotes. Nature Genetics 24 108109. (https://doi.org/10.1038/72749)

  • Wakayama T & Yanagimachi R 2001 Effect of cytokinesis inhibitors, DMSO and the timing of oocyte activation on mouse cloning using cumulus cell nuclei. Reproduction 122 4960. (https://doi.org/10.1530/rep.0.1220049)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Walther TC, Alves A, Pickersgill H, Loïodice I, Hetzer M, Galy V, Hülsmann BB, Köcher T, Wilm M & Allen T et al.2003 The conserved Nup107-160 complex is critical for nuclear pore complex assembly. Cell 113 195206. (https://doi.org/10.1016/s0092-8674(0300235-6)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wan LB, Pan H, Hannenhalli S, Cheng Y, Ma J, Fedoriw A, Lobanenkov V, Latham KE, Schultz RM & Bartolomei MS 2008 Maternal depletion of CTCF reveals multiple functions during oocyte and preimplantation embryo development. Development (Cambridge, England) 135 27292738. (https://doi.org/10.1242/dev.024539)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wassarman PM & Josefowicz WJ 1978 Oocyte development in the mouse: an ultrastructural comparison of oocytes isolated at various stages of growth and meiotic competence. Journal of Morphology 156 209235. (https://doi.org/10.1002/jmor.1051560206)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wen D, Banaszynski LA, Liu Y, Geng F, Noh KM, Xiang J, Elemento O, Rosenwaks Z, Allis CD & Rafii S 2014 Histone variant H3.3 is an essential maternal factor for oocyte reprogramming. Proceedings of the National Academy of Sciences of the United States of America 111 73257330. (https://doi.org/10.1073/pnas.1406389111)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wutz G, Várnai C, Nagasaka K, Cisneros DA, Stocsits RR, Tang W, Schoenfelder S, Jessberger G, Muhar M & Hossain MJ et al.2017 Topologically associating domains and chromatin loops depend on cohesin and are regulated by CTCF, WAPL, and PDS5 proteins. EMBO Journal 36 35733599. (https://doi.org/10.15252/embj.201798004)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Xia W, Xu J, Yu G, Yao G, Xu K, Ma X, Zhang N, Liu B, Li T & Lin Z et al.2019 Resetting histone modifications during human parental-to-zygotic transition. Science (New York, NY) 365 353360. (https://doi.org/10.1126/science.aaw5118)

    • Search Google Scholar
    • Export Citation
  • Xie SQ, Leeke BJ, Whilding C, Wagner RT, Garcia-Llagostera F, Low Y, Chammas P, Cheung NT-F, Dormann D & McManus MT et al.2022 Nucleolar-based Dux repression is essential for embryonic two-cell stage exit. Genes and Development 36 331347. (https://doi.org/10.1101/gad.349172.121)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Xiong Z, Xu K, Lin Z, Kong F, Wang Q, Quan Y, Sha QQ, Li F, Zou Z & Liu L et al.2022 Ultrasensitive Ribo-seq reveals translational landscapes during mammalian oocyte-to-embryo transition and pre-implantation development. Nature Cell Biology 24 968980. (https://doi.org/10.1038/s41556-022-00928-6)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Yamauchi Y, Ward MA & Ward WS 2009 Asynchronous DNA replication and origin licensing in the mouse one-cell embryo. Journal of Cellular Biochemistry 107 214223. (https://doi.org/10.1002/jcb.22117)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Yang G, Zhang L, Liu W, Qiao Z, Shen S, Zhu Q, Gao R, Wang M, Wang M & Li C et al.2021 Dux-mediated corrections of aberrant H3K9ac during 2-cell genome activation optimize efficiency of somatic cell nuclear transfer. Cell Stem Cell 28 150163.e5. (https://doi.org/10.1016/j.stem.2020.09.006)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Yang H, Shi L, Wang BA, Liang D, Zhong C, Liu W, Nie Y, Liu J, Zhao J & Gao X et al.2012 Generation of genetically modified mice by oocyte injection of androgenetic haploid embryonic stem cells. Cell 149 605617. (https://doi.org/10.1016/j.cell.2012.04.002)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Yang L, Liu X, Song L, Di A, Su G, Bai C, Wei Z & Li G 2020 Transient Dux expression facilitates nuclear transfer and induced pluripotent stem cell reprogramming. EMBO Reports 21 e50054. (https://doi.org/10.15252/embr.202050054)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Zaret KS 2020 Pioneer transcription factors initiating gene network changes. Annual Review of Genetics 54 367385. (https://doi.org/10.1146/annurev-genet-030220-015007)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Zhang B, Zheng H, Huang B, Li W, Xiang Y, Peng X, Ming J, Wu X, Zhang Y & Xu Q et al.2016 Allelic reprogramming of the histone modification H3K4me3 in early mammalian development. Nature 537 553557. (https://doi.org/10.1038/nature19361)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Zhang K, Wu DY, Zheng H, Wang Y, Sun QR, Liu X, Wang LY, Xiong WJ, Wang Q & Rhodes JDP et al.2020 Analysis of genome architecture during SCNT reveals a role of cohesin in impeding minor ZGA. Molecular Cell 79 234250.e9. (https://doi.org/10.1016/j.molcel.2020.06.001)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Zhang X, Li T, Zhang L, Jiang L, Cui T, Yuan X, Wang C, Liu Z, Zhang Y & Li W et al.2018 Individual blastomeres of 4- and 8-cell embryos have ability to develop into a full organism in mouse. Journal of Genetics and Genomics = Yi Chuan Xue Bao 45 677680. (https://doi.org/10.1016/j.jgg.2018.07.012)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Zhao K, Wang M, Gao S & Chen J 2021 Chromatin architecture reorganization during somatic cell reprogramming. Current Opinion in Genetics and Development 70 104114. (https://doi.org/10.1016/j.gde.2021.07.006)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Zuccotti M, Ponce RH, Boiani M, Guizzardi S, Govoni P, Scandroglio R, Garagna S & Redi CA 2002 The analysis of chromatin organisation allows selection of mouse antral oocytes competent for development to blastocyst. Zygote (Cambridge, England) 10 7378. (https://doi.org/10.1017/s0967199402002101)

    • PubMed
    • Search Google Scholar
    • Export Citation

 

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     An official journal of

    Society for Reproduction and Fertility

 

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    Figure 1

    The scheme summarizes the current knowledge on the changes occurring with the oocyte growth around the time of fertilization and early embryogenesis. During the growth phase, oocytes develop some specific features: they accumulate specific histone variants and establish oocyte-specific 3D genome features. At the same time, the sperm exhibits some unique features. These parental-specific genome features are generally not reconciled before the embryonic eight-cell stage following fertilization. The reprograming and remodeling activity is typically confined to the nucleus at stages with a low MPF activity. It gradually disappears with the loss of totipotency.

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    Figure 2

    The effect and outcome of SCNT on different types of cytoplasts. The major driving force of the remodeling activity seems to be the MPF activity. Under its influence, the nucleus disassembles, which likely results in the availability of the structural nuclear components and specific remodeling factors (darker pink). This also influences the extent of somatic material removal (green) and exchange for the oocyte/embryonic materials.

  • Bersaglieri C & Santoro R 2019 Genome Organization in and around the Nucleolus. Cells 8 579. (https://doi.org/10.3390/cells8060579)

  • Bizhanova A & Kaufman PD 2021 Close to the edge: heterochromatin at the nucleolar and nuclear peripheries. Biochimica et Biophysica Acta. Gene Regulatory Mechanisms 1864 194666. (https://doi.org/10.1016/j.bbagrm.2020.194666)

    • Search Google Scholar
    • Export Citation
  • Borensztein M, Syx L, Ancelin K, Diabangouaya P, Picard C, Liu T, Liang JB, Vassilev I, Galupa R & Servant N et al.2017 Xist-dependent imprinted X inactivation and the early developmental consequences of its failure. Nature Structural and Molecular Biology 24 226233. (https://doi.org/10.1038/nsmb.3365)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Borsos M, Perricone SM, Schauer T, Pontabry J, de Luca KL, de Vries SS, Ruiz-Morales ER, Torres-Padilla ME & Kind J 2019 Genome-lamina interactions are established de novo in the early mouse embryo. Nature 569 729733. (https://doi.org/10.1038/s41586-019-1233-0)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bouniol-Baly C, Hamraoui L, Guibert J, Beaujean N, Szöllösi MS & Debey P 1999 Differential transcriptional activity associated with chromatin configuration in fully grown mouse germinal vesicle oocytes. Biology of Reproduction 60 580587. (https://doi.org/10.1095/biolreprod60.3.580)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Buganim Y, Faddah DA & Jaenisch R 2013 Mechanisms and models of somatic cell reprogramming. Nature Reviews. Genetics 14 427439. (https://doi.org/10.1038/nrg3473)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bui HT, Wakayama S, Kishigami S, Kim JH, Van Thuan N & Wakayama T 2008 The cytoplasm of mouse germinal vesicle stage oocytes can enhance somatic cell nuclear reprogramming. Development (Cambridge, England) 135 39353945. (https://doi.org/10.1242/dev.023747)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bultman SJ, Gebuhr TC, Pan H, Svoboda P, Schultz RM & Magnuson T 2006 Maternal BRG1 regulates zygotic genome activation in the mouse. Genes and Development 20 17441754. (https://doi.org/10.1101/gad.1435106)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Burke LJ, Zhang R, Bartkuhn M, Tiwari VK, Tavoosidana G, Kurukuti S, Weth C, Leers J, Galjart N & Ohlsson R et al.2005 CTCF binding and higher order chromatin structure of the H19 locus are maintained in mitotic chromatin. EMBO Journal 24 32913300. (https://doi.org/10.1038/sj.emboj.7600793)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Burton A & Torres-Padilla ME 2014 Chromatin dynamics in the regulation of cell fate allocation during early embryogenesis. Nature Reviews. Molecular Cell Biology 15 723734. (https://doi.org/10.1038/nrm3885)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Carvalhal S, Stevense M, Koehler K, Naumann R, Huebner A, Jessberger R & Griffis ER 2017 ALADIN is required for the production of fertile mouse oocytes. Molecular Biology of the Cell 28 24702478. (https://doi.org/10.1091/mbc.E16-03-0158)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Chagin VO, Stear JH & Cardoso MC 2010 Organization of DNA replication. Cold Spring Harbor Perspectives in Biology 2 a000737. (https://doi.org/10.1101/cshperspect.a000737)

    • Search Google Scholar
    • Export Citation
  • Cheloufi S, Elling U, Hopfgartner B, Jung YL, Murn J, Ninova M, Hubmann M, Badeaux AI, Ang CE & Tenen D et al.2015 The histone chaperone CAF-1 safeguards somatic cell identity. Nature 528 218224. (https://doi.org/10.1038/nature15749)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Chen M, Zhu Q, Li C, Kou X, Zhao Y, Li Y, Xu R, Yang L, Yang L & Gu L et al.2020 Chromatin architecture reorganization in murine somatic cell nuclear transfer embryos. Nature Communications 11 1813. (https://doi.org/10.1038/s41467-020-15607-z)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Chen X, Ke Y, Wu K, Zhao H, Sun Y, Gao L, Liu Z, Zhang J, Tao W & Hou Z et al.2019 Key role for CTCF in establishing chromatin structure in human embryos. Nature 576 306310. (https://doi.org/10.1038/s41586-019-1812-0)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Chen Z, Xie Z & Zhang Y 2021 DPPA2 and DPPA4 are dispensable for mouse zygotic genome activation and pre-implantation development. Development (Cambridge, England) 148 dev200178. (https://doi.org/10.1242/dev.200178)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Chen Z & Zhang Y 2019 Loss of DUX causes minor defects in zygotic genome activation and is compatible with mouse development. Nature Genetics 51 947951. (https://doi.org/10.1038/s41588-019-0418-7)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Chouinard LA 1971 A light- and electron-microscope study of the nucleolus during growth of the oocyte in the prepubertal mouse. Journal of Cell Science 9 637663. (https://doi.org/10.1242/jcs.9.3.637)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Conti M & Franciosi F 2018 Acquisition of oocyte competence to develop as an embryo: integrated nuclear and cytoplasmic events. Human Reproduction Update 24 245266. (https://doi.org/10.1093/humupd/dmx040)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Dahl JA, Jung I, Aanes H, Greggains GD, Manaf A, Lerdrup M, Li G, Kuan S, Li B & Lee AY et al.2016 Broad histone H3K4me3 domains in mouse oocytes modulate maternal-to-zygotic transition. Nature 537 548552. (https://doi.org/10.1038/nature19360)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • De Iaco A, Planet E, Coluccio A, Verp S, Duc J & Trono D 2017 aDUX-family transcription factors regulate zygotic genome activation in placental mammals. Nature Genetics 49 941945. (https://doi.org/10.1038/ng.3858)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Dequeker BJH, Scherr MJ, Brandão HB, Gassler J, Powell S, Gaspar I, Flyamer IM, Lalic A, Tang W & Stocsits R et al.2022 MCM complexes are barriers that restrict cohesin-mediated loop extrusion. Nature 606 197203. (https://doi.org/10.1038/s41586-022-04730-0)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Dossin F & Heard E 2022 The molecular and nuclear dynamics of X-chromosome inactivation. Cold Spring Harbor Perspectives in Biology 14 a040196. (https://doi.org/10.1101/cshperspect.a040196)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Du Z, Zheng H, Huang B, Ma R, Wu J, Zhang X, He J, Xiang Y, Wang Q & Li Y et al.2017 Allelic reprogramming of 3D chromatin architecture during early mammalian development. Nature 547 232235. (https://doi.org/10.1038/nature23263)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Eckersley-Maslin M, Alda-Catalinas C, Blotenburg M, Kreibich E, Krueger C & Reik W 2019 Dppa2 and Dppa4 directly regulate the Dux-driven zygotic transcriptional program. Genes and Development 33 194208. (https://doi.org/10.1101/gad.321174.118)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Egli D & Eggan K 2010 Recipient cell nuclear factors are required for reprogramming by nuclear transfer. Development (Cambridge, England) 137 19531963. (https://doi.org/10.1242/dev.046151)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Egli D, Sandler VM, Shinohara ML, Cantor H & Eggan K 2009 Reprogramming after chromosome transfer into mouse blastomeres. Current Biology 19 14031409. (https://doi.org/10.1016/j.cub.2009.06.065)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Flyamer IM, Gassler J, Imakaev M, Brandão HB, Ulianov SV, Abdennur N, Razin SV, Mirny LA & Tachibana-Konwalski K 2017 Single-nucleus Hi-C reveals unique chromatin reorganization at oocyte-to-zygote transition. Nature 544 110114. (https://doi.org/10.1038/nature21711)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Fortin JP & Hansen KD 2015 Reconstructing A/B compartments as revealed by Hi-C using long-range correlations in epigenetic data. Genome Biology 16 180. (https://doi.org/10.1186/s13059-015-0741-y)