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.