Authors
Mandrekar, PranotiUMass Chan Affiliations
Department of Medicine, Division of GastroenterologyDocument Type
Journal ArticlePublication Date
2011-05-28Keywords
Epigenesis, GeneticEthanol
Gene Expression
Humans
Liver
Liver Diseases, Alcoholic
Oxidative Stress
Life Sciences
Medicine and Health Sciences
Women's Studies
Metadata
Show full item recordAbstract
Alcoholic liver disease (ALD) is characterized by steatosis or fat deposition in the liver and inflammation, which leads to cirrhosis and hepatocellular carcinoma. Induction of target genes without involving changes in DNA sequence seems to contribute greatly to liver injury. Chromatin modifications including alterations in histones and DNA, as well as post-transcriptional changes collectively referred to as epigenetic effects are altered by alcohol. Recent studies have pointed to a significant role for epigenetic mechanisms at the nucleosomal level influencing gene expression and disease outcome in ALD. Specifically, epigenetic alterations by alcohol include histone modifications such as changes in acetylation and phosphorylation, hypomethylation of DNA, and alterations in miRNAs. These modifications can be induced by alcohol-induced oxidative stress that results in altered recruitment of transcriptional machinery and abnormal gene expression. Delineating these mechanisms in initiation and progression of ALD is becoming a major area of interest. This review summarizes key epigenetic mechanisms that are dysregulated by alcohol in the liver. Alterations by alcohol in histone and DNA modifications, enzymes related to histone acetylation such as histone acetyltransferases, histone deacetylases and sirtuins, and methylation enzymes such as DNA methyltransferases are discussed. Chromatin modifications and miRNA alterations that result in immune cell dysfunction contributing to inflammatory cytokine production in ALD is reviewed. Finally, the role of alcohol-mediated oxidative stress in epigenetic regulation in ALD is described. A better understanding of these mechanisms is crucial for designing novel epigenetic based therapies to ameliorate ALD.Source
World J Gastroenterol. 2011 May 28;17(20):2456-64. Link to article on publisher's siteDOI
10.3748/wjg.v17.i20.2456Permanent Link to this Item
http://hdl.handle.net/20.500.14038/50996PubMed ID
21633650Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.3748/wjg.v17.i20.2456