Hypoxia response element (HRE)

Hypoxia response elements (HREs) are short, conserved DNA sequences (often with the consensus core: 5'-RCGTG-3', e.g., 5'-CGTG-3') located in the promoters/enhancers of hypoxia-inducible genes[2][7][9]. They enable binding of the HIF-1 transcription factor complex, which is a heterodimer of the oxygen-regulated HIF-1α and the constitutively expressed HIF-1β (ARNT)[1][2][7]. Under low oxygen, HIF-1α stabilizes, partners with HIF-1β, and the complex binds to HREs, increasing transcription of genes such as VEGF (angiogenesis), erythropoietin (erythropoiesis), glycolytic enzymes, and others essential for cellular adaptation to hypoxia[7][5][9]. HREs themselves are not protein targets, but rather genomic motifs recognized by HIF-1 and related factors, making them crucial for understanding hypoxic gene regulation but inappropriate as direct therapeutic targets[2][5][9].

Other names

Hypoxia-inducible factor 1 response elementHIF-1 binding site