The RNA m6A reader YTHDC1 silences retrotransposons and guards ES cell identity
Top Cited Papers
- 3 March 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature
- Vol. 591 (7849), 322-326
- https://doi.org/10.1038/s41586-021-03313-9
Abstract
The RNA modification N6-methyladenosine (m6A) has critical roles in many biological processes1,2. However, the function of m6A in the early phase of mammalian development remains poorly understood. Here we show that the m6A reader YT521-B homology-domain-containing protein 1 (YTHDC1) is required for the maintenance of mouse embryonic stem (ES) cells in an m6A-dependent manner, and that its deletion initiates cellular reprogramming to a 2C-like state. Mechanistically, YTHDC1 binds to the transcripts of retrotransposons (such as intracisternal A particles, ERVK and LINE1) in mouse ES cells and its depletion results in the reactivation of these silenced retrotransposons, accompanied by a global decrease in SETDB1-mediated trimethylation at lysine 9 of histone H3 (H3K9me3). We further demonstrate that YTHDC1 and its target m6A RNAs act upstream of SETDB1 to repress retrotransposons and Dux, the master inducer of the two-cell stage (2C)-like program. This study reveals an essential role for m6A RNA and YTHDC1 in chromatin modification and retrotransposon repression.This publication has 55 references indexed in Scilit:
- STAR: ultrafast universal RNA-seq alignerBioinformatics, 2012
- Embryonic stem cell potency fluctuates with endogenous retrovirus activityNature, 2012
- Fast gapped-read alignment with Bowtie 2Nature Methods, 2012
- Genomic Maps of Long Noncoding RNA Occupancy Reveal Principles of RNA-Chromatin InteractionsMolecular Cell, 2011
- RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genomeBMC Bioinformatics, 2011
- Integrative genomics viewerNature Biotechnology, 2011
- Simple Combinations of Lineage-Determining Transcription Factors Prime cis-Regulatory Elements Required for Macrophage and B Cell IdentitiesMolecular Cell, 2010
- The Sequence Alignment/Map format and SAMtoolsBioinformatics, 2009
- Small RNAs in transcriptional gene silencing and genome defenceNature, 2009
- Epigenetic restriction of embryonic cell lineage fate by methylation of Elf5Nature, 2008