H3K9 acetylation in the promoter-proximal region in high-fat diet fed mouse liver

Genome-wide analysis of H3K9ac in the liver of mice fed a control or a high-fat diet, and asked whether this histone mark associates with changes in gene expression. We found that over 70% of RNAPII peaks in promoter-proximal regions overlapped with H3K9ac, consistent with a role of H3K9ac in the regulation of transcription. When comparing high-fat with control diet, approximately 17% of the differentially expressed genes were associated with changes in H3K9ac in their promoters, showing a strong correlation between changes in H3K9ac signal and gene expression. Overall, our data indicate that in response to a high-fat diet, dysregulated gene expression of a subset of genes may be attributable to changes in transcription elongation driven by H3K9ac. Our results point at an added mechanism of gene regulation that may be important in the development of metabolic diseases. Citation: Morral N, Liu S, Conteh AM, Chu X, Wang Y, Dong XC, Liu Y, Linnemann AK, Wan J. Aberrant gene expression induced by a high fat diet is linked to H3K9 acetylation in the promoter-proximal region. Biochim Biophys Acta Gene Regul Mech. 2021 Mar;1864(3):194691. doi: 10.1016/j.bbagrm.2021.194691. Epub 2021 Feb 6. PMID: 33556624; PMCID: PMC7933127. Mice (n=4) were fed a high-fat (HFD, 60% kcal fat) or a control diet (CD, 18% kcal fat) for 10 weeks. Sonicated chromatin from liver tissue was immunoprecipitated with an antibody to H3K9ac, and DNA was subjected to massive parallel sequencing. H3K9ac is associated with transcription activity, and peaks were expected to overlap with areas of open chromatin. To identify these areas, ATAC-seq was carried out in control diet-fed livers.To investigate the relationship between H3K9ac signal and gene expression levels transcript abundance was determined by RNA-seq (polyA).