Li, Y and Xia, L and Tan, K and Ye, X and Zuo, Z and Li, M and Xiao, R andWang, Z and Liu, X and Deng, M and Cui, J and Yang, M and Luo, Q and Liu, Sand Cao, X and Zhu, H and Liu, T and Hu, J and Shi, J and Xiao, S
A dynamic epigenome is critical for appropriate gene expression in development and health. Central to this is the intricate process of transcription, which integrates cellular signaling with chromatin changes, transcriptional machinery and modifications to messenger RNA, such as N-methyladenosine (mA), which is co-transcriptionally incorporated. The integration of these aspects of the dynamic epigenome, however, is not well understood mechanistically. Here we show that the repressive histone mark H3K9me2 is specifically removed by the induction of mA-modified transcripts. We demonstrate that the methyltransferase METTL3/METTL14 regulates H3K9me2 modification. We observe a genome-wide correlation between mA and occupancy by the H3K9me2 demethylase KDM3B, and we find that the mA reader YTHDC1 physically interacts with and recruits KDM3B to mA-associated chromatin regions, promoting H3K9me2 demethylation and gene expression. This study establishes a direct link between mA and dynamic chromatin modification and provides mechanistic insight into the co-transcriptional interplay between RNA modifications and histone modifications.