A dynamic epigenome is critical for appropriate gene expression in development and health^1,2,3,4,5. Central to this is the intricate process of transcription^{6,7,8,9,10,11}, which integrates cellular signaling with chromatin changes, transcriptional machinery and modifications to messenger RNA, such as N⁶-methyladenosine (m⁶A), 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 m⁶A-modified transcripts. We demonstrate that the methyltransferase METTL3/METTL14 regulates H3K9me2 modification. We observe a genome-wide correlation between m⁶A and occupancy by the H3K9me2 demethylase KDM3B, and we find that the m⁶A reader YTHDC1 physically interacts with and recruits KDM3B to m⁶A-associated chromatin regions, promoting H3K9me2 demethylation and gene expression. This study establishes a direct link between m⁶A and dynamic chromatin modification and provides mechanistic insight into the co-transcriptional interplay between RNA modifications and histone modifications.

动态表观基因组对于发育和健康中的适当基因表达至关重要^1,2,3,4,5。其核心是复杂的转录过程^{6,7,8,9,10,11}，它将细胞信号与染色质变化、转录机制和对信使 RNA 的修饰整合在一起，例如N ⁶ -甲基腺苷 (m ⁶ A)，是共转录的。然而，动态表观基因组的这些方面的整合在机制上并没有得到很好的理解。在这里我们表明抑制性组蛋白标记 H3K9me2 通过 m ⁶的诱导被特异性去除A-修改的成绩单。我们证明甲基转移酶 METTL3/METTL14 调节 H3K9me2 修饰。我们观察到 m ⁶ A 与 H3K9me2 去甲基化酶 KDM3B 占据的全基因组相关性，我们发现 m ⁶ A 阅读器 YTHDC1 与 KDM3B 发生物理相互作用并将 KDM3B 招募到 m ⁶ A 相关染色质区域，促进 H3K9me2 去甲基化和基因表达. 这项研究建立了 m ⁶ A 和动态染色质修饰之间的直接联系，并提供了对 RNA 修饰和组蛋白修饰之间共转录相互作用的机制洞察。