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N6-methyladenosine RNA modification regulates embryonic neural stem cell self-renewal through histone modifications.

GSE104686 Mus musculus Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing; Other 35 samples Submitted 2017/11/21 Platform GPL9185
Summary
Internal N6-methyladenosine (m6A) modification is widespread in messenger RNAs(mRNAs) and catalyzed by heterodimers of methyltransferase-like protein 3 (Mettl3) andMettl14. To understand the role of m6A in development, we deleted Mettl14 in embryonicneural stem cells (NSCs) in a mouse model. Phenotypically, NSCs lacking Mettl14 displaymarkedly decreased proliferation and premature differentiation, suggesting m6Amodification enhances NSC self-renewal. Decreased NSC pool led to decreased numberlate-born neurons during cortical neurogenesis. Mechanistically, we discovered a genomewide increase in specific histone modifications in Mettl14 knockout vs. control NSCs. Thesechanges correlated with altered gene expression and observed cellular phenotypes,suggesting their functional significance. Finally, we showed that m6A regulates histonemodification in part by destabilizing transcripts encoding histone-modifying enzymes. Ourstudy demonstrated an essential role of m6A in development and revealed m6A-regulatedhistone modifications as a novel gene regulatory mechanism in mammalian cells.
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Also filed as BioProject PRJNA413499 and SRA study SRP119514. Searching any of these in the dataset finder brings you back here.

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