Science, Vol.367, No.6477, 580-+, 2020
N-6-methyladenosine of chromosome-associated regulatory RNA regulates chromatin state and transcription
N-6-methyladenosine (m(6)A) regulates stability and translation of messenger RNA (mRNA) in various biological processes. In this work, we show that knockout of the m(6)A writer Mettl3 or the nuclear reader Ythdc1 in mouse embryonic stem cells increases chromatin accessibility and activates transcription in an m(6)A-dependent manner. We found that METTL3 deposits m(6)A modifications on chromosome-associated regulatory RNAs (carRNAs), including promoter-associated RNAs, enhancer RNAs, and repeat RNAs. YTHDC1 facilitates the decay of a subset of these m(6)A-modified RNAs, especially elements of the long interspersed element-1 family, through the nuclear exosome targeting-mediated nuclear degradation. Reducing m(6)A methylation by METTL3 depletion or site-specific m(6)A demethylation of selected carRNAs elevates the levels of carRNAs and promotes open chromatin state and downstream transcription. Collectively, our results reveal that m(6)A on carRNAs can globally tune chromatin state and transcription.