ArticleThe Journal of biological chemistry2009
Genome-wide association of hypoxia-inducible factor (HIF)-1alpha and HIF-2alpha DNA binding with expression profiling of hypoxia-inducible transcripts.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 353 papers.
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Who cites it
353 citing papers in PubMed.
- Article
- Gut microbial remodeling as an ecological strategy for host metabolic management under environmental stress on the Xizang Plateau.BMC microbiology · 2026Article
- Kidney-specific HIF-1α-dependent ARL10/miR-1271-5p overexpression in clear cell renal cell carcinoma.British journal of cancer · 2026Article
- The cistrome response to hypoxia in human umbilical vein endothelial cells.bioRxiv : the preprint server for biology · 2026Article
- Aging Impairs Macrophage Phagocytosis Through Mitochondrial ROS-Induced Collagen Production.Aging cell · 2026Article
- ZNF395 Is a Hypoxia-Responsive Regulator of Mitochondrial Glutaminolysis in Clear Cell Renal Cell Carcinoma.Cancer research · 2026Article
- ADH1C Down-Regulation Is a Key Hypoxia Response in Colon Epithelium.The American journal of pathology · 2026Article
- <p>Regulatory networks of HIFs in tumor‑infiltrating immune cells: From molecular mechanisms to therapeutic implications (Review)</p>.International journal of oncology · 2026Review
- Multimodal bHLH-PAS DNA binding controls specificity and drives obesity.Nucleic acids research · 2026Article
- Role of trained immunity in DCs and macrophages in the induction of Th2 responses and allergy treatment. What do we know?Frontiers in immunology · 2026Review
- Exploring the genetic footprints of high altitude adapted humans and livestock.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Review
- Inherent single-cell heterogeneity of the transcriptional response to hypoxia in cancer cells.NAR cancer · 2025Article
- Interaction of TFAP2A with the Ku70/80 complex is crucial for HIF-dependent activation of hypoxia-inducible genes.The FEBS journal · 2025Article
- Pyruvate Carboxylase in Macrophages Aggravates Atherosclerosis by Regulating Metabolism Reprogramming to Promote Inflammatory Responses Through the Hypoxia-Inducible Factor-1 Signaling Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Are Hippocampal Hypoperfusion and ATP Depletion Prime Movers in the Genesis of Alzheimer's Disease? A Review of Recent Pertinent Observations from Molecular Biology.International journal of molecular sciences · 2025Review
- Cytogenetic signatures favoring metastatic organotropism in colorectal cancer.Nature communications · 2025Article
- Limiting Premenstrual Endometrial Hypoxia Inducible Factor 2 Alpha May Fine-Tune Endometrial Function at Menstruation.The Journal of clinical endocrinology and metabolism · 2025Article
- Tumour hypoxia in driving genomic instability and tumour evolution.Nature reviews. Cancer · 2025Review
- HIF1α controls steroidogenesis under acute hypoxic stress.Cell communication and signaling : CCS · 2025Article
- Decoding Sepsis: Unraveling Key Signaling Pathways for Targeted Therapies.Research (Washington, D.C.) · 2025Review
293 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors.
Funding
Abstract
Hypoxia-inducible factor (HIF) controls an extensive range of adaptive responses to hypoxia. To better understand this transcriptional cascade we performed genome-wide chromatin immunoprecipitation using antibodies to two major HIF-alpha subunits, and correlated the results with genome-wide transcript profiling. Within a tiled promoter array we identified 546 and 143 sequences that bound, respectively, to HIF-1alpha or HIF-2alpha at high stringency. Analysis of these sequences confirmed an identical core binding motif for HIF-1alpha and HIF-2alpha (RCGTG) but demonstrated that binding to this motif was highly selective, with binding enriched at distinct regions both upstream and downstream of the transcriptional start. Comparison of HIF-promoter binding data with bidirectional HIF-dependent changes in transcript expression indicated that whereas a substantial proportion of positive responses (>20% across all significantly regulated genes) are direct, HIF-dependent gene suppression is almost entirely indirect. Comparison of HIF-1alpha- versus HIF-2alpha-binding sites revealed that whereas some loci bound HIF-1alpha in isolation, many bound both isoforms with similar affinity. Despite high-affinity binding to multiple promoters, HIF-2alpha contributed to few, if any, of the transcriptional responses to acute hypoxia at these loci. Given emerging evidence for biologically distinct functions of HIF-1alpha versus HIF-2alpha understanding the mechanisms restricting HIF-2alpha activity will be of interest.
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