The RNA N6-methyladenosine regulates chromatin remodeling and transcription [seq_histoneChIP]

The N6-methyladenosine (m6A) has been shown to regulate stability and translation of messenger RNA (mRNA) in various biological processes. Here, we show that the knockout of the m6A writer Mettl3 or a nuclear reader Ythdc1 in mouse embryonic stem cells (mESCs) induces chromatin openness and transcription activation in an m6A-dependent manner. We identified extensive m6A modifications on caRNAs (chromosome-associated RNAs, including promoter-associated RNAs, enhancer RNAs and repeats) that are installed by METTL3. YTHDC1 can bind to a portion of these m6A-modified RNAs and facilitate their decay through the NEXT-mediated nuclear degradation. Therefore, the m6A methylation of these caRNAs reduces their abundances. The knockout of Mettl3 elevates levels of caRNAs and promote open chromatin state and downstream transcription. Collectively, our results reveal that m6A on caRNAs can globally tune chromatin state and transcription. Examination of H3K27ac and H3K4me3 modifications in three cell types.