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| Status |
Public on Nov 15, 2017 |
| Title |
Regulation of the transition from mitosis to meiosis by the conserved RNA-helicase YTHDC2/BGCN [RIP-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
In the germline stem cell lineage, proliferating gonial cells switch from mitotic proliferation to meiotic prophase, marked by the onset of a cell-type-specific transcription program and a specialized cell cycle required to generate haploid gametes. The Drosophila gene benign gonial cell neoplasm (bgcn) encodes an RNA binding translational repressor required in fly testes for spermatogonia to stop dividing and transition to the spermatocyte state and meiosis. Here we show that the mammalian bgcn ortholog, YTHDC2, plays a key role in allowing a clean transition from mitosis to meiosis in both male and female germ cells in mouse, pointing towards a conserved role of post-transcriptional control of RNA translation and/or stability in this critical cell fate transition. Ythdc2-/- male germ cells undergo mitotic divisions but fail to properly execute meiotic prophase, instead attempting a mitotic-like division then undergoing cell death. Many meiotic markers were only weakly expressed in Ythdc2-/- testes compared to wild-type controls. Strikingly, the mitotic cyclin Cyclin A2, which is down-regulated prior to entry into meiotic prophase in wild-type, remained high in Ythdc2-/- germ cells that also expressed the meiotic marker SYCP3, suggesting that the mutant germ cells attempting to enter meiotic prophase have a mixed identity. YTHDC2 binds RNAs involved in both the mitotic cell cycle, including the mRNA Ccna2 that encodes Cyclin A2, as well as specific piRNA precursor RNAs and transcripts required for later stages of germ cell differentiation. YTHDC2-bound RNAs in testes were enriched for the m6A modification, suggesting that YTHDC2 may selectively regulate multiple target RNAs marked with m6A, to promote a clean transition from mitosis to meiosis and terminal differentiation.
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| Overall design |
mRNA profiles for wild-type and YTHDC2/BGCN testis at P12 and P14 were generated by sequencing. m6A modified transcripts were identified by immunopreciitation with an anti-m6A specific antibody followed by sequencing for P12 testes. RNAs interacting with YTHDC2/BGCN were identified by immunoprecipitation with a anti-YTHDC2/BGCN specific antibody followe by sequencing for P12 testes. All experiments were performed in duplicates.
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| Contributor(s) |
Bailey AS, Batista PJ, Gold RS, Chen YG, de Rooij DG, Chang HY, Fuller MT |
| Citation(s) |
29087293 |
| |
| Submission date |
Jan 12, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Pedro J Batista |
| E-mail(s) |
pedro.batista@nih.gov
|
| Phone |
3014356294
|
| Organization name |
National Institutes of Health
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| Department |
National Cancer Institute
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| Lab |
Cell Biology
|
| Street address |
37 Convent Street Bldg 37
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| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE93567 |
Regulation of the transition from mitosis to meiosis by the conserved RNA-helicase YTHDC2/BGCN |
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| Relations |
| BioProject |
PRJNA361125 |
| SRA |
SRP096653 |
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