Dynamic Control of Chromatin-associated m6A Methylation Regulates Nascent RNAs Stability [ChIP-seq]

N6-methyladenosine (m6A) has been shown to regulate various aspects of mRNA biology. Although m6A has been shown to be co-transcriptionally deposited in mRNA by the chromatin-bound methyltranferase METTL3, the precise role of METTL3 and the resulting m6A methylation remain incompletely understood. Here, we demonstrate that the nascent RNAs generated from enhancers and promoters are co-transcriptionally and dynamically regulated by the chromatin bound METTL3/14 methyltransferase complex, and the demethylase, ALKBH5. Importantly, nascent RNA m6A is recognized by the reader protein hnRNP G, which prevents access of the RNA endonuclease INTS11 and thus protects nascent RNA from inappropriate degradation. Our study thus reveals an important chromatin function of m6A in stabilizing the enhancer- and promoter-derived nascent RNAs, which function to promote transcription activation. Examination of METTL3/METTL14/WTAP/ALKBH5/hnRNP G binding and histone modifications.