Hypoxia-inducible factor 1 alpha activates and is inhibited by unoccupied estrogen receptor beta.
Previously, we showed that hypoxia induces ligand-independent estrogen receptor (ER)alpha activation. In this study, we found that hypoxia activated the ER beta-mediated transcriptional response in HEK293 cells in the absence of estrogen. ER beta transactivation was induced by the expression of the hypoxia-inducible factor 1 alpha (HIF-1 alpha) under normoxia. ER beta interacted with HIF-1 alpha, and SRC1 and CBP potentiated the effect of HIF-1 alpha on ER beta-mediated transcription. We then examined the effect of ER beta on HIF1-alpha transactivation. Surprisingly, ER beta attenuated the transcriptional activity of HIF-1 alpha, as measured by HRE-driven reporter gene expression and hypoxic induction of VEGF mRNA in HEK293 cells. Taken together, these data show that HIF-1 alpha activates ER beta-mediated transcription in the absence of a ligand, and ER beta inhibits HIF-1 alpha-mediated transcription.
Lim
Wonchung
W
College of Life Science, Institute of Biotechnology, Department of Bioscience and Biotechnology, Sejong University, Kwang-Jin-Gu, Seoul 143-747, Republic of Korea.
Cho
Jungyoon
J
Kwon
Hyeok-yi
HY
Park
Yeomyeong
Y
Rhyu
Mee-Ra
MR
Lee
YoungJoo
Y
D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D047629:Estrogen Receptor beta / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
D017931:DNA Primers; D047629:Estrogen Receptor beta; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A