Heterogeneity in binding and gene-expression regulation by HIF-2alpha.
Here, we demonstrate by chromatin immunoprecipitation that the binding of hypoxia-inducible factors to gene regulatory regions is differentially influenced in cancer cells. Binding of HIF-2alpha varies depending on hypoxic conditions, although HIF-1alpha is constantly bound to these regions. We found by RNA interference experiments that HIF-2alpha plays a minor role in VEGF gene upregulation under hypoxia or CoCl(2) treatment, even when both HIFs are similarly bound to the promoter region. HIF-2alpha activated or suppressed the ENO1 gene under various conditions, irrespective of promoter binding. We additionally found that HIF dependence on EPO gene induction could be altered depending on the conditions, irrespective of the binding pattern of HIFs. These results demonstrate that, unlike HIF-1alpha, HIF-2alpha differentially binds and regulates transcription under hypoxia.
Koizume
Shiro
S
Molecular Pathology & Genetics Division, Kanagawa Cancer Center Research Institute, 1-1-2 Nakao, Asahi-ku, Yokohama 241-0815, Japan.
Yokota
Naho
N
Miyagi
Etsuko
E
Hirahara
Fumiki
F
Tsuchiya
Eiju
E
Miyagi
Yohei
Y
D000693:Anaerobiosis / Q000235:genetics; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D003035:Cobalt / Q000494:pharmacology; D004921:Erythropoietin / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D005786:Gene Expression Regulation; D006801:Humans; D010100:Oxygen / Q000378:metabolism; D011401:Promoter Regions, Genetic; D015533:Transcriptional Activation; D000099162:Endothelial PAS Domain-Containing Protein 1
D051792:Basic Helix-Loop-Helix Proteins; D003035:Cobalt; D004921:Erythropoietin; D010100:Oxygen; D000099162:Endothelial PAS Domain-Containing Protein 1; C018021:cobaltous chloride