ArticleAmerican journal of physiology. Regulatory, integrative and comparative physiology2013
Promoter methylation of Egr-1 site contributes to fetal hypoxia-mediated PKCε gene repression in the developing heart.
Article in American journal of physiology. Regulatory, integrative and comparative physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 26 citations in OpenAlex.
- Insights from animal models: Dissecting the independent roles of oxygen and nutrients in the fetal origins of cardiovascular disease.The Journal of physiology · 2026Review
- Early growth response-1: Key mediators of cell death and novel targets for cardiovascular disease therapy.Frontiers in cardiovascular medicine · 2023Review
- Chronic hypoxia alters cardiac mitochondrial complex protein expression and activity in fetal guinea pigs in a sex-selective manner.American journal of physiology. Regulatory, integrative and comparative physiology · 2021Article
- Single molecule characterization of the binding kinetics of a transcription factor and its modulation by DNA sequence and methylation.Nucleic acids research · 2021Article
- Sex differences and the effects of intrauterine hypoxia on growth and in vivo heart function of fetal guinea pigs.American journal of physiology. Regulatory, integrative and comparative physiology · 2020Article
- EGR-mediated control of STIM expression and function.Cell calcium · 2019Review
- Cardiovascular Programming During and After Diabetic Pregnancy: Role of Placental Dysfunction and IUGR.Frontiers in endocrinology · 2019Review
- Gestational Hypoxia and Developmental Plasticity.Physiological reviews · 2018Review
- Chronic hypoxia upregulates DNA methyltransferase and represses large conductance Ca2+-activated K+ channel function in ovine uterine arteries.Biology of reproduction · 2017Article
- The programming of cardiovascular disease.Journal of developmental origins of health and disease · 2015Review
- Structural impact of complete CpG methylation within target DNA on specific complex formation of the inducible transcription factor Egr-1.FEBS letters · 2015Article
- Estrogen Regulates Angiotensin II Receptor Expression Patterns and Protects the Heart from Ischemic Injury in Female Rats.Biology of reproduction · 2015Article
- Litter and sex effects on maternal behavior and DNA methylation of the Nr3c1 exon 17 promoter gene in hippocampus and cerebellum.International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience · 2014Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Fetal hypoxia causes protein kinase Cε (PKCε) gene repression in the heart resulting in heightened ischemic injury in male offspring in a sex-dependent manner. The present study tested the hypothesis that heightened methylation of the early growth response factor-1 (Egr-1) binding site at PKCε gene promoter contributes to sex dimorphism of hypoxia-induced programming of PKCε gene repression in the developing heart. Pregnant rats were divided into normoxic and hypoxic (10.5% O2 from day 15 to 21 of gestation) groups. Hypoxia selectively decreased PKCε mRNA and protein abundance in the heart of male, but not female, near-term (21 days) fetuses. Methylation of the CpG site at the Egr-1 binding site of PKCε promoter was significantly increased in the male hearts by hypoxia, resulting in decreased Egr-1 binding affinity and reduced Egr-1 binding to the PKCε promoter. Nuclear Egr-1 levels were not affected by hypoxia. There was significantly higher abundance of estrogen receptor α (ERα) and β (ERβ) isoforms in female than in male fetal hearts, which were not significantly altered by hypoxia. Both ERα and ERβ bind to the Egr-1 binding site with significant greater levels in the female fetal hearts. The increased methylation with reduced Egr-1 binding and PKCε gene repression persisted in 3-mo-old adult male hearts in a sex-dependent manner. The results indicate a key role for heightened methylation of the Egr-1 binding site in hypoxia-mediated programming of PKCε gene repression in the developing heart and suggest a novel protective mechanism of ER by binding to the Egr-1 binding site in epigenetic regulation of PKCε gene expression patterns in the early developmental stage.
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