title: Acetylation of histone H3 at lysine 9 by ethanol in rat hepatocytes.
abstract: Histone acetylation plays an important role in transcriptional activation. We have investigated the effect of ethanol on nuclear histone H3 acetylation in rat hepatocytes. Hepatocytes were incubated with ethanol (5-200 mM) for 24h and then acetylation states of nuclear histone H3 at specific lysine residues (Lys(9) and Lys(14)) were measured by immunoblot analysis using site-specific antibodies. Ethanol increased acetylation of histone H3 at Lys(9) in a dose-dependent manner; 3-fold at 5mM and maximum of 8-fold at 100mM. Sensitivity to low dose of ethanol was remarkable. This ethanol-induced acetylation was also time-dependent, showing a maximal response at 24h. Ethanol did not alter the level of histone H3 expression. Trichostatin A, a histone deacetylase inhibitor, was used as a positive control and it also increased acetylation. However, acetylation at Lys(14) was not affected by ethanol. Treatment of cells with ethanol metabolizing enzyme inhibitors (4-methylpyrazole and cyanamide) decreased ethanol-induced histone H3 acetylation at Lys(9). This is the first report of ethanol-induced selective, post-translational acetylation of histone H3 at Lys(9). This is not due to increased histone expression or a direct physical effect of ethanol but is dependent on ethanol metabolism.
authors.affiliation: Department of Medical Pharmacology and Physiology, School of Medicine, University of Missouri at Columbia, One Hospital Drive, Rm. M517B Med. Sci. Bldg., Columbia, MO 65212, USA.
authors.forename: Pil-Hoon
authors.initials: PH
authors.lastname: Park
authors.forename: Rebecca
authors.initials: R
authors.lastname: Miller
authors.forename: Shivendra D
authors.initials: SD
authors.lastname: Shukla
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D003484:Cyanamide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006877:Hydroxamic Acids / Q000494:pharmacology; D015151:Immunoblotting; D008239:Lysine / Q000737:chemistry; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014158:Transcription, Genetic
chemical_list: D006657:Histones; D006877:Hydroxamic Acids; D011500:Protein Synthesis Inhibitors; D000431:Ethanol; C012589:trichostatin A; D003484:Cyanamide; D006655:Histone Deacetylases; D008239:Lysine