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Egr1 plays a key role in fetal programming of gender‐dependent PKCε gene expression patterns in the developing heart
Author(s) -
Chen Man,
Zhang Lubo
Publication year - 2012
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.26.1_supplement.699.4
Subject(s) - fetus , biology , egr1 , hypoxia (environmental) , methylation , endocrinology , offspring , medicine , gene expression , dna methylation , psychological repression , cpg site , protein kinase c , promoter , andrology , gene , signal transduction , chemistry , microbiology and biotechnology , pregnancy , genetics , organic chemistry , oxygen
Fetal hypoxia resulted in PKCε gene repression in the heart leading to the heightened heart susceptibility to ischemic injury in adult male offspring. The present study examined the role of Egr1 in hypoxia‐mediated PKCε gene repression. Pregnant rats were divided into normoxic and hypoxic (10.5% O2 from day 15 to 21 of gestation) groups. The male and female progeny were studied at 21 day of gestation and 3 months of age. Hypoxia significantly decreased PKCε mRNA and protein abundance in male fetal and offspring hearts. In accordance, CpG methylation of the Egr1 binding site at PKCε promoter was significantly increased in male hearts by hypoxia. Methylation of the Egr1 binding site significantly decreased Egr1 binding to the promoter. In fetal hearts, there was significantly greater abundance of estrogen receptor α (ERα) and β (ERβ) isoforms in females than in males. Both ERα and ERβ interacted more with the Egr1 binding site in the female fetal hearts than in males in both normoxic and hypoxic groups. The results indicate a key role for CpG methylation of Egr1 binding site in hypoxia‐mediated and gender‐dependent PKCε gene repression in the developing heart, and suggest a possible protective role of ER in fetal programming of aberrant gene expression patterns in the heart. (Supported in part by NIH grants HL82779 and HL83966).