May 18, 2022 · H3K36me2/3 does not counteract docking of PRC2 onto histone H3 but, rather, inhibits its catalytic activity [170, 179]. Through mutagenesis analysis, a H3K36me-sensing motif—D 630 PVQK 634 —was uncovered on the catalytic EZH2 subunit of PRC2.

To address this, we mapped the endogenous interactomes of Ezh2 and Suz12 in embryonic stem cells (ESCs), and we combined this with a functional screen for H3K27 methylation marks. We found that Nsd1-mediated H3K36me2 co-locates with H3K27me2, and its loss leads to genome-wide expansion of H3K27me3.

In this review, we focus on the H3K36-specific histone methyltransferases in metazoans, and discuss their enzymatic activity regulation and their roles in antagonizing Polycomb silencing and safeguarding transcription fidelity. Keywords: H3K36 methylation, Histone methyltransferase, SETD2, Ash1L, NSD.

Jul 17, 2023 · At a cellular level, H3K36M facilitates epithelial plasticity by rendering fibroblasts insensitive to TGFβ signals. At a molecular level, H3K36M enables the decommissioning of mesenchymal...

Apr 19, 2018 · We found that Nsd1-mediated H3K36me2 co-locates with H3K27me2, and its loss leads to genome-wide expansion of H3K27me3. These increases in H3K27me3 occurred at PRC2/PRC1 target genes and as de novo accumulation within what were previously broad H3K27me2 domains.

Jan 8, 2025 · To functionally test this regulatory model, we treated H3K36M-expressing organoids with vehicle control (dimethylsulfoxide, DMSO) or inhibitors of PRC2 components EED (EED226) or EZH2 (GSK126).

Jun 7, 2021 · Mechanistically, NSD1 regulates Sox9 expression by modulating H3K36me1 and H3K36me2 levels in the Sox9 promoter region, constituting a novel epigenetic regulatory mechanism of chondrogenesis.

Sep 4, 2014 · In this study, we demonstrate interplay between two oncogenic proteins, MMSET and EZH2, known to methylate histone H3 on lysine 36 (H3K36) and lysine 27 (H3K27), respectively.

Nov 19, 2020 · Here, the cryo-EM structure of PRC2 on dinucleosomes reveals how binding of its catalytic subunit EZH2 to nucleosomal DNA orients the H3 N-terminus via an extended network of interactions to place H3K27 into the active site. Unmodified H3K36 occupies a critical position in the EZH2-DNA interface.

H3K36me2/3 has been proposed to influence PRC2 function in several ways: H3K36me3 has been shown to inhibit PRC2 catalytic activity in vitro, but has also been suggested as a potential recruitment mechanism to transcribed chromatin via recognition by the Tudor domains of …