Obesity increases histone H3 lysine 9 and 18 acetylation at Tnfa and Ccl2 genes in mouse liver

Obesity contributes to the development of non-alcoholic fatty liver disease (NAFLD), which is characterized by the upregulated expression of two key inflammatory mediators: tumor necrosis factor (Tnfa) and monocyte chemotactic protein 1 (Mcp1; also known as Ccl2). However, the chromatin make-up at t...

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Bibliographic Details
Published in:International journal of molecular medicine 2014-12, Vol.34 (6), p.1647-1654
Main Authors: MIKULA, MICHAL, MAJEWSKA, ANETA, LEDWON, JOANNA KAROLINA, DZWONEK, ARTUR, OSTROWSKI, JERZY
Format: Article
Language:English
Subjects:
Analysis
Cell culture
Chromatin
chromatin immunoprecipitation
Complications and side effects
Epigenetics
Gene expression
Genes
Genetic aspects
histone H3 acetylation
Inflammation
Kinases
Laboratories
lipopolysaccharides
Liver diseases
liver steatosis
Lysine
Metabolism
Obesity
Phosphatase
Physiological aspects
Proteins
Risk factors
Studies
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Summary:Obesity contributes to the development of non-alcoholic fatty liver disease (NAFLD), which is characterized by the upregulated expression of two key inflammatory mediators: tumor necrosis factor (Tnfa) and monocyte chemotactic protein 1 (Mcp1; also known as Ccl2). However, the chromatin make-up at these genes in the liver in obese individuals has not been explored. In this study, to identify obesity-mediated epigenetic changes at Tnfa and Ccl2, we used a murine model of obesity induced by a high-fat diet (HFD) and hyperphagic (ob/ob) mice. Chromatin immunoprecipitation (ChIP) assay was used to determine the abundance of permissive histone marks, namely histone H3 lysine 9 and 18 acetylation (H3K9/K18Ac), H3 lysine 4 trimethylation (H3K4me3) and H3 lysine 36 trimethylation (H3K36me3), in conjunction with polymerase 2 RNA (Pol2) and nuclear factor (NF)-κB recruitment in the liver. Additionally, to correlate the liver tissue-derived ChIP measurements with a robust in vitro transcriptional response at the Tnfa and Ccl2 genes, we used lipopolysaccharide (LPS) treatment to induce an inflammatory response in Hepa1-6 cells, a cell line derived from murine hepatocytes. ChIP revealed increased H3K9/K18Ac at Tnfa and Ccl2 in the obese mice, although the differences were only statistically significant for Tnfa (P
ISSN:1107-3756
1791-244X
DOI:10.3892/ijmm.2014.1958