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

Ziwei Dai, Samantha J. Mentch, Xia Gao, Sailendra N. Nichenametla and Jason W. Locasale ()
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Ziwei Dai: Duke University School of Medicine
Samantha J. Mentch: Duke University School of Medicine
Xia Gao: Duke University School of Medicine
Sailendra N. Nichenametla: Orentreich Foundation for the Advancement of Science
Jason W. Locasale: Duke University School of Medicine

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-04426-y

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