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Katharine Cecchini RNA Therapeutics Institute and Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, Massachusetts, USA

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Adriano Biasini RNA Therapeutics Institute and Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, Massachusetts, USA

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Tianxiong Yu Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, Massachusetts, USA

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Martin Säflund Department of Molecular Biosciences, The Wenner–Gren Institute, Stockholm University, Stockholm, Sweden

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Haiwei Mou Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA

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Amena Arif RNA Therapeutics Institute and Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, Massachusetts, USA
Beam Therapeutics, Cambridge, Massachusetts, USA

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Atiyeh Eghbali Department of Molecular Biosciences, The Wenner–Gren Institute, Stockholm University, Stockholm, Sweden

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Cansu Colpan RNA Therapeutics Institute and Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, Massachusetts, USA
Voyager Therapeutics, Cambridge, Massachusetts, USA

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Ildar Gainetdinov RNA Therapeutics Institute and Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, Massachusetts, USA

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Dirk G de Rooij Reproductive Biology Group, Division of Developmental Biology, Department of Biology, Faculty of Science, Utrecht University, Utrecht, The Netherlands

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Zhiping Weng Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, Massachusetts, USA

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Phillip D Zamore RNA Therapeutics Institute and Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, Massachusetts, USA

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Deniz M Özata Department of Molecular Biosciences, The Wenner–Gren Institute, Stockholm University, Stockholm, Sweden

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In brief

The testis-specific transcription factor, TCFL5, expressed in pachytene spermatocytes regulates the meiotic gene expression program in collaboration with the transcription factor A-MYB.

Abstract

In male mice, the transcription factors STRA8 and MEISON initiate meiosis I. We report that STRA8/MEISON activates the transcription factors A-MYB and TCFL5, which together reprogram gene expression after spermatogonia enter into meiosis. TCFL5 promotes the transcription of genes required for meiosis, mRNA turnover, miR-34/449 production, meiotic exit, and spermiogenesis. This transcriptional architecture is conserved in rhesus macaque, suggesting TCFL5 plays a central role in meiosis and spermiogenesis in placental mammals. Tcfl5em1/em1 mutants are sterile, and spermatogenesis arrests at the mid- or late-pachytene stage of meiosis. Moreover, Tcfl5+/em1 mutants produce fewer motile sperm.

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