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Methionine metabolism influences the genomic architecture of H3K4me3 with the link to gene expression encoded in peak width

View ORCID ProfileZiwei Dai, View ORCID ProfileSamantha J. Mentch, Xia Gao, Sailendra N. Nichenametla, View ORCID ProfileJason W. Locasale
doi: https://doi.org/10.1101/243196
Ziwei Dai
1Department of Pharmacology and Cancer Biology, Duke Molecular Physiology Institute, Duke Cancer Institute, Duke University School of Medicine, Durham, NC 27710, USA
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Samantha J. Mentch
1Department of Pharmacology and Cancer Biology, Duke Molecular Physiology Institute, Duke Cancer Institute, Duke University School of Medicine, Durham, NC 27710, USA
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Xia Gao
1Department of Pharmacology and Cancer Biology, Duke Molecular Physiology Institute, Duke Cancer Institute, Duke University School of Medicine, Durham, NC 27710, USA
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Sailendra N. Nichenametla
2Orentreich Foundation for the Advancement of Science, Cold Spring, NY 10516
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Jason W. Locasale
1Department of Pharmacology and Cancer Biology, Duke Molecular Physiology Institute, Duke Cancer Institute, Duke University School of Medicine, Durham, NC 27710, USA
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  • For correspondence: jason.locasale@duke.edu
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Abstract

Nutrition and metabolism are known to influence chromatin biology and epigenetics by modifying the levels of post-translational modifications on histones, yet how changes in nutrient availability influence specific aspects of genomic architecture and connect to gene expression is unknown. To investigate this question we considered, 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 analyzed the genome-wide changes in H3K4me3 and gene expression in response to alterations in methionine availability under conditions that are known to affect the global levels of histone methylation in both normal rodent physiology and in human cancer cells. Surprisingly, we found that the location of H3K4me3 peaks at specific genomic loci was largely preserved under conditions of methionine restriction. However, upon examining different geometrical features of peak shape, it was found that the response of H3K4me3 peak width encoded almost all aspects of H3K4me3 biology including changes in expression levels, and the presence of cell identity and cancer associated genes. These findings reveal simple yet new and profound principles for how nutrient availability modulates specific aspects of chromatin dynamics to mediate key biological features.

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Posted January 05, 2018.
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Methionine metabolism influences the genomic architecture of H3K4me3 with the link to gene expression encoded in peak width
Ziwei Dai, Samantha J. Mentch, Xia Gao, Sailendra N. Nichenametla, Jason W. Locasale
bioRxiv 243196; doi: https://doi.org/10.1101/243196
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Methionine metabolism influences the genomic architecture of H3K4me3 with the link to gene expression encoded in peak width
Ziwei Dai, Samantha J. Mentch, Xia Gao, Sailendra N. Nichenametla, Jason W. Locasale
bioRxiv 243196; doi: https://doi.org/10.1101/243196

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