Hypoxia-inducible factor 1α activates and is inhibited by unoccupied estrogen receptor β

Previously, we showed that hypoxia induces ligand-independent estrogen receptor (ER)α activation. In this study, we found that hypoxia activated the ERβ-mediated transcriptional response in HEK293 cells in the absence of estrogen. ERβ transactivation was induced by the expression of the hypoxia-inducible factor 1α (HIF-1α) under normoxia. ERβ interacted with HIF-1α, and SRC1 and CBP potentiated the effect of HIF-1α on ERβ-mediated transcription. We then examined the effect of ERβ on HIF1-α transactivation. Surprisingly, ERβ attenuated the transcriptional activity of HIF-1α, as measured by HRE-driven reporter gene expression and hypoxic induction of VEGF mRNA in HEK293 cells. Taken together, these data show that HIF-1α activates ERβ-mediated transcription in the absence of a ligand, and ERβ inhibits HIF-1α-mediated transcription.