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Mol. Biosci."],"abstract":"<jats:p>Studies indicate that induction of metabolic gene expression by nutrient intake, and in response to subsequently secreted hormones, is regulated by transcription factors binding to cis-elements and associated changes of epigenetic memories (histone modifications and DNA methylation) located in promoter and enhancer regions. Carbohydrate intake-mediated induction of metabolic gene expression is regulated by histone acetylation and the histone acetylation reader bromodomain-containing protein 4 (BRD4) on the gene body region, which corresponds to the transcribed region of the gene. In this review, we introduce carbohydrate-responsive metabolic gene regulation by (i) transcription factors and epigenetic memory in promoter\/enhancer regions (promoter\/enhancer-based epigenetics), and (ii) histone acetylation and BRD4 in the gene body region (gene body-based epigenetics). Expression of carbohydrate-responsive metabolic genes related to nutrient digestion and absorption, fat synthesis, inflammation in the small intestine, liver and white adipose tissue, and in monocytic\/macrophage-like cells are regulated by various transcription factors. The expression of these metabolic genes are also regulated by transcription elongation <jats:italic>via<\/jats:italic> histone acetylation and BRD4 in the gene body region. Additionally, the expression of genes related to fat synthesis, and the levels of acetylated histones and BRD4 in fat synthesis-related genes, are downregulated in white adipocytes under insulin resistant and\/or diabetic conditions. In contrast, expression of carbohydrate-responsive metabolic genes and\/or histone acetylation and BRD4 binding in the gene body region of these genes, are upregulated in the small intestine, liver, and peripheral leukocytes (innate leukocytes) under insulin resistant and\/or diabetic conditions. In conclusion, histone acetylation and BRD4 binding in the gene body region as well as transcription factor binding in promoter\/enhancer regions regulate the expression of carbohydrate-responsive metabolic genes in many metabolic organs. Insulin resistant and diabetic conditions induce the development of metabolic diseases, including type 2 diabetes, by reducing the expression of BRD4-targeted carbohydrate-responsive metabolic genes in white adipose tissue and by inducing the expression of BRD4-targeted carbohydrate-responsive metabolic genes in the liver, small intestine, and innate leukocytes including monocytes\/macrophages and neutrophils.<\/jats:p>","DOI":"10.3389\/fmolb.2021.682696","type":"journal-article","created":{"date-parts":[[2021,7,15]],"date-time":"2021-07-15T14:35:10Z","timestamp":1626359710000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Regulation of Carbohydrate-Responsive Metabolic Genes by Histone Acetylation and the Acetylated Histone Reader BRD4 in the Gene Body Region"],"prefix":"10.3389","volume":"8","author":[{"given":"Kazuki","family":"Mochizuki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiori","family":"Ishiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natsuyo","family":"Hariya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshinao","family":"Goda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,7,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1016\/s0304-4165(98)00150-0","article-title":"Disordered Expression of the Sucrase-Isomaltase Complex in the Small Intestine in Otsuka Long-Evans Tokushima Fatty Rats, a Model of Non-insulin-dependent Diabetes Mellitus with Insulin Resistance","volume":"1426","author":"Adachi","year":"1999","journal-title":"Biochim. 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