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Chronic ethanol intake leads to differential effects on the multivalent epigenetic state in liver (1120.1)
Author(s) -
Patra Biswanath,
Kuttippurathu Lakshmi,
Hoek Jan,
Vadigepalli Rajanikanth
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1120.1
Subject(s) - chromatin immunoprecipitation , epigenetics , histone h3 , histone , acetylation , methylation , western blot , promoter , calorie , biology , blot , histone methylation , medicine , dna methylation , endocrinology , chemistry , biochemistry , gene expression , gene
The objective of this study was to characterize the effects of chronic alcohol consumption on the epigenetic state of key regulators of liver function, repair and regeneration. Rats were fed a liquid diet following established Lieber‐DeCarli protocol, with the treatment group of animals receiving 36% of total calories derived from ethanol, and pair‐fed control animals receiving an iso‐caloric liquid diet, for 5 weeks or 7 months. Chromatin immunoprecipitation (ChIP) and high‐throughput RT‐PCR assays were performed to test the level of H3K27me3, H3K9me2, H3K9ac, H3K18ac at a selected target promoters, using Diagenode autoChIP protocols. Expression of H3 methyl and acetyl protein was tested by Western blotting. Overall histone acetylation and methylation levels were found to be decreased at both 5 week and 7 month time points as revealed by Western blot assays. However, nearly all of the histone markers tested showed differential methylation and acetylation, with significant increase at several key target promoters, at either 5 week or 7 month time frame of chronic ethanol intake. Our results reveal a combinatorial epigenetic state in which multiple histone modification markers were enriched at several target promoters, and the patterns of these multivalent states were altered in a complex manner during adaptation to chronic ethanol intake. Research Support: NIH R01 AA018873, K05 AA017261, and T32 AA007463.