【摘 要】
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N6-methyladenosine (m6A) on chromosome-associated regulatory RNAs (carRNAs),including repeat RNAs,plays important roles in tuning the chromatin state and transc
【机 构】
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Institute for Regenerative Medicine,Shanghai East Hospital,Shanghai Key Laboratory of Signaling and
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N6-methyladenosine (m6A) on chromosome-associated regulatory RNAs (carRNAs),including repeat RNAs,plays important roles in tuning the chromatin state and transcription,but the intrinsic mechanism remains unclear.Here,we report that YTHDC1 plays indispens-able roles in the self-renewal and differentiation potency of mouse embryonic stem cells (ESCs),which highly depends on the m6A-binding ability.Ythdc1 is required for sufficient rRNA synthesis and repression of the 2-cell (2C) transcriptional program in ESCs,which recapitulates the transcriptome regulation by the LINE1 scaffold.Detailed analyses revealed that YTHDC1 rec-ognizes m6A on LINE1 RNAs in the nucleus and regulates the formation of the LINE1-NCL partnership and the chromatin recruitment of KAP1.Moreover,the establishment of H3K9me3 on 2C-related retrotrans-posons is interrupted in Ythdc1-depleted ESCs and inner cell mass (ICM) cells,which consequently increa-ses the transcriptional activities.Our study reveals a role of m6A in regulating the RNA scaffold,providing a new model for the RNA-chromatin cross-talk.
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