The transcription factor TCFL5 responds to A-MYB to elaborate the male meiotic program in mice

Author:

Cecchini Katharine1,Biasini Adriano1,Yu Tianxiong2,Säflund Martin3,Mou Haiwei4,Arif Amena15,Eghbali Atiyeh3,Colpan Cansu16,Gainetdinov Ildar1,de Rooij Dirk G7,Weng Zhiping2,Zamore Phillip D1ORCID,Özata Deniz M3ORCID

Affiliation:

1. RNA Therapeutics Institute and Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, Massachusetts, USA

2. Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, Massachusetts, USA

3. Department of Molecular Biosciences, The Wenner–Gren Institute, Stockholm University, Stockholm, Sweden

4. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA

5. Beam Therapeutics, Cambridge, Massachusetts, USA

6. Voyager Therapeutics, Cambridge, Massachusetts, USA

7. Reproductive Biology Group, Division of Developmental Biology, Department of Biology, Faculty of Science, Utrecht University, Utrecht, The Netherlands

Abstract

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.

Publisher

Bioscientifica

Subject

Cell Biology,Obstetrics and Gynecology,Endocrinology,Embryology,Reproductive Medicine

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