Gene-selective histone H3 acetylation in the absence of increase in global histone acetylation in liver of rats chronically fed alcohol.
OBJECTIVE
The aim of this study was to determine the effect of chronic ethanol feeding on acetylation of histone H3 at lysine 9 (H3-Lys9) at promoter and coding regions of genes for class I alcohol dehydrogenase (ADH I), inducible nitric oxide synthase (iNOS), Bax, p21, c-met and hepatocyte growth factor in the rat liver.


METHODS
Rats were fed ethanol-containing liquid diet (5%, w/v) for 1-4 weeks. The global level of acetylation of H3-Lys9 in the liver was examined by western blot analysis. The levels of mRNA for various genes were measured by real-time reverse transcriptase-polymerase chain reaction. The association of acetylated histone H3-Lys9 with the different regions of genes was monitored by chromatin immunoprecipitation assay.


RESULTS
Chronic ethanol treatment increased mRNA expression of genes for iNOS, c-jun and ADH 1. Chronic ethanol treatment did not cause increase in global acetylation of H3-Lys9, but significantly increased the association of acetylated histone H3-Lys9 in the ADH I gene, both in promoter and in coding regions. In contrast, chronic ethanol treatment did not significantly increase the association of acetylated histone H3-Lys9 with iNOS and c-jun genes.


CONCLUSIONS
Chronic ethanol exposure increased the gene-selective association of acetylated H3-Lys9 in the absence of global histone acetylation. Thus, not all genes expressed by ethanol are linked to transcription via histone H3 acetylation at Lys9.
College of Pharmacy, Yeungnam University, Gyeongsan, Gyeongsangbuk-do, Republic of Korea.
Pil-Hoon
PH
Park
Robert W
RW
Lim
Shivendra D
SD
Shukla
D000107:Acetylation / Q000187:drug effects; D000426:Alcohol Dehydrogenase / Q000187:drug effects / Q000235:genetics; D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D016758:Genes, jun / Q000187:drug effects; D017228:Hepatocyte Growth Factor / Q000235:genetics; D006657:Histones / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008239:Lysine; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D019859:Proto-Oncogene Proteins c-met / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051028:bcl-2-Associated X Protein / Q000187:drug effects / Q000235:genetics
D002492:Central Nervous System Depressants; D006657:Histones; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D000431:Ethanol; D017228:Hepatocyte Growth Factor; D000426:Alcohol Dehydrogenase; D052247:Nitric Oxide Synthase Type II; D019859:Proto-Oncogene Proteins c-met; D008239:Lysine