title: Probing the epigenetic regulation of HIF-1α transcription in developing tissue.
abstract: HIF-1 is the master regulator of cellular hypoxia response; the oxygen sensitive HIF-1α subunit transactivates its own expression in hypoxia via a hypoxia response element (HRE) in the promoter of the HIF-1α gene. This transactivation loop significantly contributes to the build up of HIF-1α at the onset of hypoxia, with the binding of HIF-1 to the HIF-1α promoter being dependent on the epigenetic status of a CpG dinucleotide in the upstream HRE. Given the central role played by HIF-1 in tissue development, we sought to probe the epigenetic status of the HIF-1α HRE and that of its downstream target EPO in embryonic tissue. Our data shows that the CpG dinucleotide in HIF-1α HRE is unmethylated in several embryonic tissue samples, suggesting that transactivation of HIF-1α plays a significant role in HIF-1 mediated hypoxia response during development.
authors.affiliation: Chemistry, University of Southampton, Southampton, SO17 1BJ, UK. a.tavassoli@soton.ac.uk.
authors.forename: I N
authors.initials: IN
authors.lastname: Mistry
authors.forename: P J S
authors.initials: PJ
authors.lastname: Smith
authors.forename: D I
authors.initials: DI
authors.lastname: Wilson
authors.forename: A
authors.initials: A
authors.lastname: Tavassoli
mesh_terms: D015687:Cell Hypoxia; D018899:CpG Islands; D019175:DNA Methylation; D004622:Embryo, Mammalian / Q000166:cytology* / Q000378:metabolism; D044127:Epigenesis, Genetic; D004921:Erythropoietin / Q000235:genetics*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D045325:HCT116 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D061986:MCF-7 Cells; D011247:Pregnancy; D011401:Promoter Regions, Genetic
chemical_list: C554270:EPO protein, human; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D004921:Erythropoietin