Methionine metabolism influences genomic architecture and gene expression through H3K4me3 peak width

Nature Communications
Ziwei DaiJason W Locasale

Abstract

Nutrition and metabolism are known to influence chromatin biology and epigenetics through post-translational modifications, yet how this interaction influences genomic architecture and connects to gene expression is unknown. Here we consider, as a model, the metabolically-driven dynamics of H3K4me3, a histone methylation mark that is known to encode information about active transcription, cell identity, and tumor suppression. We analyze the genome-wide changes in H3K4me3 and gene expression in response to alterations in methionine availability in both normal mouse physiology and human cancer cells. Surprisingly, we find that the location of H3K4me3 peaks is largely preserved under methionine restriction, while the response of H3K4me3 peak width encodes almost all aspects of H3K4me3 biology including changes in expression levels, and the presence of cell identity and cancer-associated genes. These findings may reveal general principles for how nutrient availability modulates specific aspects of chromatin dynamics to mediate biological function.

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Citations

Dec 7, 2019·The Journal of Biological Chemistry·H Karimi KinyamuTrevor K Archer
Jan 27, 2019·Proceedings of the National Academy of Sciences of the United States of America·Lauren V AlbrechtEdward M De Robertis
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Feb 6, 2020·Cell Metabolism·Shuang TangJason W Locasale
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Datasets Mentioned

BETA
GSE103602

Methods Mentioned

BETA
ChIP-seq
immunoprecipitation
RNA-seq

Software Mentioned

GraphPad Prism
MUltiScale enrIchment
TopHat2
Bowtie2
MATLAB
deepTools
Integrative Genomics Viewer
GSEA
HTSeq Table Browser
Homer

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