Histone

Gene

Cell biology

Molecular biology

Methyltransferase

Biology

Epigenetics

Chromatin remodeling

Demethylase

Regulation of gene expression

Demethylation

DNA methylation

Histone code

Genetics

Chromatin

Histone methylation

Epigenome

Methylation

Histone methyltransferase

5-Hydroxymethylcytosine

Histone H3

N6-Methyladenosine

Nucleosome

Gene expression

Nature Genetics

A dynamic epigenome is critical for appropriate gene expression in development and health1–5. Central to this is the intricate process of transcription6–11, 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. METTL3-induced deposition of N6-methyladenosine (m6A) in RNA correlates with removal of H3K9me2 genome wide. The m6A reader YTHDC1 recruits the H3K9me2 demethylase KDM3B to chromatin.

N6-Methyladenosine co-transcriptionally directs the demethylation of histone H3K9me2