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Microbiota-dependent histone butyrylation in the mammalian intestine

ABSTRACT: Posttranslational modifications (PTMs) on histone proteins are a key source of regulation on chromatin through impacting genome organization and important cellular processes, including gene expression. These PTMs often arise from small metabolites and are thus impacted by cellular metabolism and environmental cues. One such class of metabolically regulated PTMs are histone acylations, which include histone acetylation, along with butyrylation, crotonylation, and propionylation. We asked whether histone acylations of intestinal epithelial cells (IECs) are regulated through the availability of short chain fatty acids (SCFAs), which are generated by the commensal microbiota in the intestinal lumen. We identified specific sites of butyrylation and propionylation on lysine 9 and 27 on histone H3. We demonstrate that these acylations are regulated by the microbiota, whereas histone butyrylation is additionally regulated by the metabolite tributyrin. Furthermore, we also identify tributyrin-regulated gene programs that correlate with histone butyrylation and demonstrate that histone butyrylation (H3K27bu) is associated with active gene regulatory elements and levels of gene expression. Together, our observations demonstrate a physiological setting in which previously uncharacterized histone acylations are dynamically regulated and associated with gene expression.

INSTRUMENT(S): Q Exactive HF, Q Exactive

ORGANISM(S): Mus Musculus (ncbitaxon:10090)

SUBMITTER: Peder Lund

PROVIDER: MSV000090586 | MassIVE | Tue Oct 25 13:40:00 BST 2022

REPOSITORIES: MassIVE

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