Bindings of ChREBP and SREBP1, and Histone Acetylation around the Rat Liver Fatty Acid Synthase Gene Are Associated with Induction of the Gene during the Suckling-Weaning Transition

Morishita, Saho; Mochizuki, Kazuki; Goda, Toshinao

doi:10.3177/jnsv.60.94

Cited by 13 publications

(9 citation statements)

References 35 publications

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“…Most importantly, the strong enhancement of SREBP1 und PPRAG protein expression in the SLC-KO mice occurred in the pericentral zone which is in line with published data from mice fed with a high fat diet ( Inoue et al, 2005 ; Liu, 2012 ). For SREBP1 it was shown that this protein has binding sites at -7000 bp and -500 bp of the Fasn gene ( Amemiya-Kudo et al, 2002 ; Morishita et al, 2014 ). Furthermore it was also shown that overexpression of SREBP1c, an isoform of SREBP1, lead to significant upregulation of Fasn gene expression in hepatocytes ( Dentin et al, 2004 ).…”

Section: Discussionmentioning

confidence: 99%

Hedgehog signaling is a potent regulator of liver lipid metabolism and reveals a GLI-code associated with steatosis

Matz‐Soja

Rennert

Schönefeld

et al. 2016

eLife

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Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in industrialized countries and is increasing in prevalence. The pathomechanisms, however, are poorly understood. This study assessed the unexpected role of the Hedgehog pathway in adult liver lipid metabolism. Using transgenic mice with conditional hepatocyte-specific deletion of Smoothened in adult mice, we showed that hepatocellular inhibition of Hedgehog signaling leads to steatosis by altering the abundance of the transcription factors GLI1 and GLI3. This steatotic 'Gli-code' caused the modulation of a complex network of lipogenic transcription factors and enzymes, including SREBP1 and PNPLA3, as demonstrated by microarray analysis and siRNA experiments and could be confirmed in other steatotic mouse models as well as in steatotic human livers. Conversely, activation of the Hedgehog pathway reversed the "Gli-code" and mitigated hepatic steatosis. Collectively, our results reveal that dysfunctions in the Hedgehog pathway play an important role in hepatic steatosis and beyond.DOI: http://dx.doi.org/10.7554/eLife.13308.001

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Section: Discussionmentioning

confidence: 99%

Hedgehog signaling is a potent regulator of liver lipid metabolism and reveals a GLI-code associated with steatosis

Matz‐Soja

Rennert

Schönefeld

et al. 2016

eLife

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“…The novel epigenetic model regulates the efficacy of mRNA synthesis, for example from 100% to 140%. Recently, our study demonstrated that high carbohydrate intake enhances histone acetylation in the gene body rather than in the promoter/enhancer region of carbohydrate-responsive genes, such as carbohydrate digestion-and absorption-related genes including sucraseisomaltase, Sglt1, and Glut5 in the small intestine (Honma et al 2013, Inoue et al 2011, and Fas in the liver during the suckling-weaning transition period of rats (Morishita et al 2014). Carbohydrate-inducible fat accumulation-related genes in the liver, such as Cyp8b1, Dak, and Plin5, are similarly regulated by BRD4 (Yamada et al 2016).…”

Section: General and Novel Epigeneticsmentioning

confidence: 87%

“…For example, expression of glycerol‐3‐phosphate acyltransferase‐1, a fatty acid synthesis‐related gene, in the liver increased and DNA methylation of the gene decreased during periods of changing diets from milk (a high fat diet) to solid food (a high carbohydrate diet) in the process of weaning mice (Ehara et al ). In addition, we have demonstrated that expression of fatty acid synthase ( Fas ) in the liver and histone acetylation of the gene increased during the suckling‐weaning transient period (Morishita et al ). It was reported that unsaturated fatty acids, which are found in milk, enhanced genes related to fatty acid oxidation by demethylating DNA in the promoter/enhancer region of genes (Ehara et al ).…”

Section: Epigenetic Evidence Of the Dohad Theory In Animal Modelsmentioning

confidence: 99%

Relationship between epigenetic regulation, dietary habits, and the developmental origins of health and disease theory

Mochizuki

Hariya

Honma

et al. 2017

Congenital Anomalies

Self Cite

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Environmental stressors during developmental stages are hypothesized to increase the risk of developing metabolic diseases such as obesity, type 2 diabetes, hypertension, and psychiatric diseases during later life. This theory is known as the Developmental Origins of Health and Disease (DOHaD). Recent studies suggest that accumulation of environmental stress, including those during developmental stages, is internalized as acquired information designated as "epigenetic memory." This epigenetic memory is generally indicated as DNA methylation and histone modifications in the chromatin. In general, the demethylation of CpG islands induces histone acetylation and associated changes from heterochromatin to euchromatin, and enhances transcriptional activation. These changes are induced by the binding of transcriptional factors to cis-elements located on promoter and enhancer regions and the associated binding of histone acetyl-transferase and the transcription initiation complex. Recent studies have demonstrated novel epigenetic modifications that regulate transcription elongation steps by activating histone acetylation and bromodomain-containing protein 4, which contains two bromodomains to bind acetylated histones, on the gene body (transcribed region). Gene expression alterations induced by carbohydrate signals and by changes in energy balance in the body are regulated by this model. In addition, induction of many metabolic genes, which are induced or reduced in adulthood by malnutrition during developmental stages, by intake of major nutrients, or development of lifestyle diseases in adulthood, are targeted by these novel epigenetic changes. In the present review, we introduce epigenetic regulations and the relationship with nutrient intake, and discuss links between epigenetic regulation and the development of metabolic diseases according to DOHaD.

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“…This is subsequently bound by positive elongation factor b (P-TEFb), which is a cyclin T1-CDK9 complex. BRD4 and the associated P-TEFb complex on the gene body region enhance transcriptional elongation by phosphorylating RNA polymerase II at the second serine residue of the C-terminal domain [12][13][14] (Figure 5B). …”

Section: Epigenetic Responses To Environmental Factorsmentioning

confidence: 99%

“…The epigenetic model of gene regulation based on histone modifications and DNA methylation in the gene body region explains the efficacy of mRNA synthesis. Our recent studies in rats have demonstrated that carbohydrate intake increases histone acetylation in the gene body region, rather than in the promoter/enhancer region, of carbohydrate metabolism-related genes, such as sucrose-isomaltase, sodium glucose transporter 1, and glucose transporter 5 in the small intestine [12,13], and fatty acid synthase in the liver during the suckling-weaning transition period [14]. In addition, we have demonstrated that fructose-inducible genes related to fat accumulation, such as Cyp8b1, Dak, and Plin5, are regulated by BRD4 in the liver [15].…”

Section: Epigenetic Responses To Environmental Factorsmentioning

confidence: 99%

Preimplantation Genetic Screening

Sermon¹

2017

obm.genet

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A number of epidemiological studies have suggested that environmental stresses, such as malnutrition during the fetal period, can induce development of metabolic disorders, such as obesity, type 2 diabetes, and hypertension, and and even psychiatric disorders in later life. This theory model is known as the Developmental Origins of Health and Disease (DOHaD) theory, in which postulates that "epigenetic memories", involving DNA methylation, histone modifications and microRNA expression, are induced by environmental stresses during development. For example, the binding of transcription factors to cis-elements within the promoters and enhancer regions of genes induces demethylation leading to and subsequent histone acetylation and transcriptional activation. Several lines of evidence suggest that binding of bromodomain-containing protein 4 and positive transcription elongation factor B to acetylated histones within "gene body" regions initiates transcriptional elongation, and while histone H3K36 methylation and DNA methylation within "gene body" these regions OBM Genetics 2017; 1(4), doi:10.21926/obm.genet.1704008Page 2/15 terminates this transcriptional elongation. This new epigenetic model of the gene body regulation can be applied to the regulation of metabolic genes, which respond to carbohydrate signals and are associated with energy balance. Recent studies indicate that these new gene body epigenetic mechanisms, as well as the classical promoter/enhancer mechanism, are responsible for regulation of epigenetic changes found in offspring that have been exposed to malnutrition during the fetal period. In this context, further understanding of epigenetic gene regulation during the fetal period based on the "gene body epigenetic model" during the fetal period should provide new preventive and therapeutic strategies for adult diseases encompassed by DOHaD theory.

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Bindings of ChREBP and SREBP1, and Histone Acetylation around the Rat Liver Fatty Acid Synthase Gene Are Associated with Induction of the Gene during the Suckling-Weaning Transition

Cited by 13 publications

References 35 publications

Hedgehog signaling is a potent regulator of liver lipid metabolism and reveals a GLI-code associated with steatosis

Hedgehog signaling is a potent regulator of liver lipid metabolism and reveals a GLI-code associated with steatosis

Relationship between epigenetic regulation, dietary habits, and the developmental origins of health and disease theory

Preimplantation Genetic Screening

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