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Biotinylation and methylation of histones play a role in regulation of genes associated with hydrogen peroxide induced oxidative stress
Author(s) -
Wijeratne Subhashinee Samudra,
Zempleni Janos
Publication year - 2008
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.22.1_supplement.689.2
Subject(s) - epigenetics , histone , histone methyltransferase , microbiology and biotechnology , gene expression , biology , chromatin immunoprecipitation , gene , promoter , regulation of gene expression , histone h3 , methylation , biochemistry
The expression of approximately 10,000 genes changed in response to oxidative stress by H 2 O 2 in Caco‐2 cells. Three genes, epidermal growth factor receptor (EGFR), the oncogene homolog KRAS, and guanidinoacetate N‐methyltransferase (GAMT), which showed the highest fold‐change in their expressions, were chosen to evaluate whether chromatin remodeling events play a role in stress‐dependent gene regulation. Relative enrichment of two epigenetic markers, biotinylation of lysine 12 in histone H4 (K12BioH4) and dimethylation of lysine 9 in histone H3 (K9Me2H3) in the promoter regions of the above genes was quantified by ChIP assays. Increased expression of EGFR and KRAS in stressed cells was associated with decreased relative abundance of K9Me2H3, whereas decreased expression of GMAT was associated with increased relative abundance of K9Me2H3 in promoter regions. The relative abundance K12BioH4 decreased in promoter regions of all three genes in stressed cells regardless of their observed expression changes, probably due to low expression of holocarboxylase synthetase (HCS), the mediator of biotinylation. These results suggest that epigenetic events may play a role in the expression of EGFR, KRAS and GMAT genes in oxidatively stressed cells. Support: Univ. of Nebraska ARD, Hatch Act, and NIH DK063945 and ES015206 , USDA 2006‐35200‐17138, and NSF EPSCoR EPS‐0701892.