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.
Highlights
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
This study possibly identifies general principles about how specific aspects of the genomic architecture of a histone mark are affected by nutrient availability
We found that H3K4me[3], a chromatin mark known to associate with active transcription, responds to methionine restriction (MR) with a global compression of peak area and height across most modified sites, which is consistent with the substantial reduction of bulk levels observed previously[22,23]
Summary
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. We find that the location of H3K4me[3] peaks is largely preserved under methionine restriction, while the response of H3K4me[3] peak width encodes almost all aspects of H3K4me[3] 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. When these modifications are known to mark key aspects of chromatin status, global changes could have broad consequences to epigenomic programs How these bulk changes to the levels of post-translational modifications on chromatin alter the genomic architecture of histone marks and relate to gene expression is, largely unknown. How metabolic dynamics that occur due to differences in nutritional status or metabolic pathway activity might affect these programs and gene activity related to H3K4me[3] is largely unknown
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