N6-Methyladenosine co-transcriptionally directs the demethylation of histone H3K9me2
N6-Methyladenosine co-transcriptionally directs the demethylation of histone H3K9me2
复制标题
N6-甲基腺苷共转录指导组蛋白 H3K9me2 去甲基化
DOI：
10.1038/s41588-020-0677-3
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发表时间：
2020-08-10
期刊：
影响因子：
30.8
通讯作者：
Xia, Laixin
中科院分区：
文献类型：
--
作者：
Li, Yuan;Xia, Linjian;Xia, Laixin
L3诱导的N（6）-甲基腺苷（m（6）A）在RNA中的沉积与H3 K9 me 2基因组范围内的去除相关。m（6）A阅读器YTHDC 1将H3 K9 me 2脱甲基酶KDM 3B募集到染色质中。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（1-5）。其核心是复杂的转录过程（6-11），它将细胞信号传导与染色质变化、转录机制和对信使RNA的修饰（如N（6）-甲基腺苷（m（6）A））整合在一起，后者以共转录方式掺入。然而，动态表观基因组的这些方面的整合在机制上还没有得到很好的理解。在这里，我们表明，抑制性组蛋白标记H3 K9 me 2是特别删除的诱导m（6）A修饰的转录本。我们证明了甲基转移酶胃L3/胃L14调节H3 K9 me 2修饰。我们观察到m（6）A和H3 K9 me 2去甲基化酶KDM 3B占据之间的全基因组相关性，我们发现m（6）A阅读器YTHDC 1与KDM 3B物理相互作用并将其招募到m（6）A相关的染色质区域，促进H3 K9 me 2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RNA修饰和组蛋白修饰之间的共转录相互作用的机制。
METTL3-induced deposition ofN(6)-methyladenosine (m(6)A) in RNA correlates with removal of H3K9me2 genome wide. The m(6)A reader YTHDC1 recruits the H3K9me2 demethylase KDM3B to chromatin.A dynamic epigenome is critical for appropriate gene expression in development and health(1-5). Central to this is the intricate process of transcription(6-11), which integrates cellular signaling with chromatin changes, transcriptional machinery and modifications to messenger RNA, such asN(6)-methyladenosine (m(6)A), 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 m(6)A-modified transcripts. We demonstrate that the methyltransferase METTL3/METTL14 regulates H3K9me2 modification. We observe a genome-wide correlation between m(6)A and occupancy by the H3K9me2 demethylase KDM3B, and we find that the m(6)A reader YTHDC1 physically interacts with and recruits KDM3B to m(6)A-associated chromatin regions, promoting H3K9me2 demethylation and gene expression. This study establishes a direct link between m(6)A and dynamic chromatin modification and provides mechanistic insight into the co-transcriptional interplay between RNA modifications and histone modifications.