H3K27M in Gliomas Causes a One-Step Decrease in H3K27 Methylation and Reduced Spreading within the Constraints of H3K36 Methylation.

Cell Reports
Ashot S HarutyunyanJacek Majewski

Abstract

The discovery of H3K27M mutations in pediatric gliomas marked a new chapter in cancer epigenomics. Numerous studies have investigated the effect of this mutation on H3K27 trimethylation, but only recently have we started to realize its additional effects on the epigenome. Here, we use isogenic glioma H3K27M+/- cell lines to investigate H3K27 methylation and its interaction with H3K36 and H3K9 modifications. We describe a "step down" effect of H3K27M on the distribution of H3K27 methylation: me3 is reduced to me2, me2 is reduced to me1, whereas H3K36me2/3 delineates the boundaries for the spread of H3K27me marks. We also observe a replacement of H3K27me2/3 silencing by H3K9me3. Using a computational simulation, we explain our observations by reduced effectiveness of PRC2 and constraints imposed on the deposition of H3K27me by antagonistic H3K36 modifications. Our work further elucidates the effects of H3K27M in gliomas as well as the general principles of deposition in H3K27 methylation.

Associated Datasets

Citations

May 11, 2021·The FEBS Journal·Shriya DeshmukhNada Jabado
Jul 16, 2021·Science Advances·Jia-Ray YuDanny Reinberg
Oct 6, 2021·Nature Reviews. Genetics·Sanne M Janssen, Matthew C Lorincz

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Datasets Mentioned

BETA
GSE147783
GSE128745

Methods Mentioned

BETA
immunoprecipitation
ChIP-seq
transfection
fluorescence-activated cell sorting
Protein assay
electrophoresis
ChIP
PCR
WGBS
RNA-seq

Software Mentioned

STAR
computeMatrix
R
Epicenter
bedtools
PELT
deepTools plotHeatmap
deepTools
STOPHIM
colorMap

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