{"doi":"10.1158/1541-7786.c.6542202","title":"Data from Differential Hypoxic Regulation of Hypoxia-Inducible Factors 1α and 2α","abstract":"&lt;div&gt;Abstract&lt;p&gt;The hypoxia-inducible transcription factors (HIF) 1α and HIF-2α play a critical role in cellular response to hypoxia. Elevated HIF-α expression correlates with poor patient survival in a large number of cancers. Recent evidence suggests that HIF-2α appears to be preferentially expressed in neuronal tumor cells that exhibit cancer stem cell characteristics. These observations suggest that expression of HIF-1α and HIF-2α is differentially regulated in the hypoxic tumor microenvironment. However, the underlying mechanisms remain to be fully investigated. In this study, we investigated the transcriptional regulation of &lt;i&gt;HIF&lt;/i&gt;-&lt;i&gt;1α&lt;/i&gt; and &lt;i&gt;HIF&lt;/i&gt;-&lt;i&gt;2α&lt;/i&gt; under different physiologically relevant hypoxic conditions. We found that transcription of &lt;i&gt;HIF&lt;/i&gt;-&lt;i&gt;2α&lt;/i&gt; was consistently increased by hypoxia, whereas transcription of &lt;i&gt;HIF&lt;/i&gt;-&lt;i&gt;1α&lt;/i&gt; showed variable levels of repression. Mechanistically, differential regulation of &lt;i&gt;HIF&lt;/i&gt;-&lt;i&gt;α&lt;/i&gt; transcription involved hypoxia-induced changes in acetylation of core histones H3 and H4 associated with the proximal promoters of the &lt;i&gt;HIF&lt;/i&gt;-&lt;i&gt;1α&lt;/i&gt; or &lt;i&gt;HIF&lt;/i&gt;-&lt;i&gt;2α&lt;/i&gt; gene. We also found that, although highly stable under acute hypoxia, HIF-1α and HIF-2α proteins become destabilized under chronic hypoxia. Our results have thus provided new mechanistic insights into the differential regulation of &lt;i&gt;HIF&lt;/i&gt;-&lt;i&gt;1α&lt;/i&gt; and &lt;i&gt;HIF&lt;/i&gt;-&lt;i&gt;2α&lt;/i&gt; by the hypoxic tumor microenvironment. These findings also suggest an important role of HIF-2α in the regulation of tumor progression under chronic hypoxia. &lt;i&gt;Mol Cancer Res; 9(6); 757–65. ©2011 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;","journal":null,"year":2023,"id":405842,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9588,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1184963,"name":"Xiangyu Cong","orcid":null,"position":1,"is_corresponding":false},{"id":1182568,"name":"Zhong Yun","orcid":"0000-0003-4123-747X","position":2,"is_corresponding":false},{"id":1182567,"name":"Qun Lin","orcid":"0000-0003-0209-6424","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:20:59.152593Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}