Systematic perturbations of SETD2, NSD1, NSD2, NSD3, and ASH1L reveal their distinct contributions to H3K36 methylation.

ABSTRACT:

Background

Methylation of histone 3 lysine 36 (H3K36me) has emerged as an essential epigenetic component for the faithful regulation of gene expression. Despite its importance in development and disease, how the molecular agents collectively shape the H3K36me landscape is unclear.

Results

We use mouse mesenchymal stem cells to perturb the H3K36me methyltransferases (K36MTs) and infer the activities of the five most prominent enzymes: SETD2, NSD1, NSD2, NSD3, and ASH1L. We find that H3K36me2 is the most abundant of the three methylation states and is predominantly deposited at intergenic regions by NSD1, and partly by NSD2. In contrast, H3K36me1/3 are most abundant within exons and are positively correlated with gene expression. We demonstrate that while SETD2 deposits most H

SUBMITTER: Shipman GA 

PROVIDER: S-EPMC11465688 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature