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Ethanol increases histone H3‐K4 methylation and decreases histone H3‐K9 acetylation in conjunction with increased p16 gene expression in the normal colonic epithelial cells
Author(s) -
Jang Hyeran,
Barlev Nickolai A.,
Ausman Lynne M.,
Mason Joel B.,
Moyer Mary P.,
Choi SangWoon
Publication year - 2009
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.23.1_supplement.555.5
Subject(s) - histone h3 , acetylation , histone , methylation , gene expression , microbiology and biotechnology , lysine , epigenetics , chemistry , histone methyltransferase , histone methylation , methionine , ezh2 , regulation of gene expression , biochemistry , dna methylation , biology , gene , amino acid
The objective of this study was to determine whether disturbances in one‐carbon metabolism could modify p16 gene expression through histone modifications. NCM460, human colonic epithelial cells, were incubated in media 1) deficient in folate, methionine and choline, 2) with 100μM Adox (adenosine‐2', 3′‐dialdehyde, an S‐adenosylhomocysteine hydrolase inhibitor), and 3) with 100mM ethanol, which inhibits methionine synthesis and reduces methyl group availability. Histone methylation at histone H3 lysine 4 (H3‐K4) and acetylation at lysine 9 (H3‐K9), both known to be increased in active genes, were measured by Western blotting and p16 gene expression by RT‐PCR. Ethanol increased H3‐K4 trimethylation (p=0.005) and decreased H3‐K9 acetylation (p<0.0001) in a time‐dependent fashion. These changes in histone modifications were paralleled with increased p16 expression (p=0.003). Adox decreased H3‐K9 acetylation time‐dependently (p=0.004) without any change in p16 expression. Folate/methionine/choline deficiency didn't produce any changes in this in vitro culture model. This study demonstrates that in this normal colonic cell line, ethanol, which inhibits one‐carbon metabolism, alters H3‐K4 trimethylation and H3‐K9 acetylation in conjunction with an increase in p16 expression. Grant Funding Source NIH R21 AA016681