The conserved RNA helicase YTHDC2 regulates the transition from proliferation to differentiation in the germline
- Stanford University School of Medicine, United States
- University of Amsterdam, Netherlands
Abstract
The switch from mitosis to meiosis is the key event marking onset of differentiation in the germline stem cell lineage. In Drosophila, the translational repressor Bgcn is required for spermatogonia to stop mitosis and transition to meiotic prophase and the spermatocyte state. Here we show that the mammalian Bgcn ortholog YTHDC2 facilitates a clean switch from mitosis to meiosis in mouse germ cells, revealing a conserved role for YTHDC2 in this critical cell fate transition. YTHDC2-deficient male germ cells enter meiosis but have a mixed identity, maintaining expression of Cyclin A2 and failing to properly express many meiotic markers. Instead of continuing through meiotic prophase, the cells attempt an abnormal mitotic-like division and die. YTHDC2 binds multiple transcripts including Ccna2 and other mitotic transcripts, binds specific piRNA precursors, and interacts with RNA granule components, suggesting that proper progression of germ cells through meiosis is licensed by YTHDC2 through post-transcriptional regulation.
Data availability
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Regulation of the transition from mitosis to meiosis by the conserved RNA-helicase YTHDC2/BGCNNCBI Gene Expression Omnibus (accession no: GSE93567).
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Poised chromatin and bivalent domains facilitate the mitosis-to-meiosis transition in the male germlineNCBI Gene Expression Omnibus (accession no: GSE69946).
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Cellular source and mechanisms of high transcriptome complexity in the mammalian testis (RNA-Seq cells)NCBI Gene Expression Omnibus (accession no: GSE43717).
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RNA-Seq and RNA Polymerase II ChIP-Seq of mouse spermatogenesisNCBI Gene Expression Omnibus (accession no: GSE44346).
Article and author information
Author details
Funding
National Institutes of Health (NIH T32 HD007249)
- Alexis S Bailey
Lalor Foundation (Postdoctoral Fellowship)
- Alexis S Bailey
National Cancer Institute (Intramural Research Program of the NIH)
- Pedro J Batista
National Institutes of Health (NIH R01 HG004361)
- Howard Y Chang
Reed-Hodgson Professorship
- Margaret T Fuller
National Institutes of Health (NIH P50 HD068158)
- Margaret T Fuller
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health (NIH). All of the experiments were approved by the Stanford University Animal Care and Use Committee (IACUC), protocol (#21656).
Human subjects: Human testis sections were obtained from the Fertility Preservation Program of Pittsburgh. Informed consent was obtained and the testicular tissue freezing protocol was approved by the Institutional Review Board of the University of Pittsburgh.
Copyright
© 2017, Bailey et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The conserved RNA helicase YTHDC2 regulates the transition from proliferation to differentiation in the germline
eLife 6:e26116.
https://doi.org/10.7554/eLife.26116
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