Gene Symbol: hif1ab
Description: hypoxia inducible factor 1 subunit alpha b
Alias: hif1a, wu:fb63a10, zgc:55405, hypoxia-inducible factor 1-alpha, HIF1B, hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor) b
Species: zebrafish
Products:     hif1ab

Top Publications

  1. Rojas D, Perez Munizaga D, Centanin L, Antonelli M, Wappner P, Allende M, et al. Cloning of hif-1alpha and hif-2alpha and mRNA expression pattern during development in zebrafish. Gene Expr Patterns. 2007;7:339-45 pubmed
    ..This is the first time that a detailed comparison of the expression of hif-1alpha and hif-2alpha is directly assessed in a vertebrate model system throughout development. ..
  2. Foley J, Yeh J, Maeder M, Reyon D, Sander J, Peterson R, et al. Rapid mutation of endogenous zebrafish genes using zinc finger nucleases made by Oligomerized Pool ENgineering (OPEN). PLoS ONE. 2009;4:e4348 pubmed publisher
  3. Kajimura S, Aida K, Duan C. Understanding hypoxia-induced gene expression in early development: in vitro and in vivo analysis of hypoxia-inducible factor 1-regulated zebra fish insulin-like growth factor binding protein 1 gene expression. Mol Cell Biol. 2006;26:1142-55 pubmed
    ..These results suggest that HIF-1 mediates hypoxia-induced IGFBP-1 gene expression in early development by selectively interacting with the -1090/-1086 HRE and its adjacent HAS. ..
  4. Elks P, Brizee S, van der Vaart M, Walmsley S, van Eeden F, Renshaw S, et al. Hypoxia inducible factor signaling modulates susceptibility to mycobacterial infection via a nitric oxide dependent mechanism. PLoS Pathog. 2013;9:e1003789 pubmed publisher
    ..Stabilization of Hif-1α therefore represents a potential target for therapeutic intervention against tuberculosis. ..
  5. Rytkönen K, Akbarzadeh A, Miandare H, Kamei H, Duan C, Leder E, et al. Subfunctionalization of cyprinid hypoxia-inducible factors for roles in development and oxygen sensing. Evolution. 2013;67:873-82 pubmed publisher
    ..These results demonstrate the subfunctionalization of cyprinid hif alpha paralogs for specialized roles in development and the hypoxic stress response. ..
  6. Santhakumar K, Judson E, Elks P, McKee S, Elworthy S, van Rooijen E, et al. A zebrafish model to study and therapeutically manipulate hypoxia signaling in tumorigenesis. Cancer Res. 2012;72:4017-27 pubmed publisher
    ..Taken together, our findings establish Vhl as a genuine tumor suppressor in zebrafish and offer this model as a tool to noninvasively study VHL and HIF signaling during tumorigenesis and development. ..
  7. Elks P, van Eeden F, Dixon G, Wang X, Reyes Aldasoro C, Ingham P, et al. Activation of hypoxia-inducible factor-1? (Hif-1?) delays inflammation resolution by reducing neutrophil apoptosis and reverse migration in a zebrafish inflammation model. Blood. 2011;118:712-22 pubmed publisher
    ..Our data demonstrate that Hif-1? regulates neutrophil function in complex ways during inflammation resolution in vivo. ..
  8. Wang J, Zhang D, Du J, Zhou C, Li Z, Liu X, et al. Tet1 facilitates hypoxia tolerance by stabilizing the HIF-? proteins independent of its methylcytosine dioxygenase activity. Nucleic Acids Res. 2017;45:12700-12714 pubmed publisher
    ..Furthermore, we found that Tet1 enhances rather than prevents poly-ubiquitination on HIF-?. Our results reveal a previously unrecognized function of Tet1 independent of its methylcytosine dioxygenase activity in hypoxia signaling. ..
  9. Guan L, Chi W, Xiao W, Chen L, He S. Analysis of hypoxia-inducible factor alpha polyploidization reveals adaptation to Tibetan Plateau in the evolution of schizothoracine fish. BMC Evol Biol. 2014;14:192 pubmed publisher

More Information


  1. Elks P, van der Vaart M, van Hensbergen V, Schutz E, Redd M, Murayama E, et al. Mycobacteria counteract a TLR-mediated nitrosative defense mechanism in a zebrafish infection model. PLoS ONE. 2014;9:e100928 pubmed publisher
    ..Shifting the balance of host-pathogen interactions in favor of the host by targeting this virulence mechanism may help to alleviate the problem of infection with Mtb strains that are resistant to multiple drug treatments. ..
  2. Kopp R, Köblitz L, Egg M, Pelster B. HIF signaling and overall gene expression changes during hypoxia and prolonged exercise differ considerably. Physiol Genomics. 2011;43:506-16 pubmed publisher
  3. Hsieh C, Ko C, Chen S, Liu T, Wu J, Hu C, et al. In vivo long-term continuous observation of gene expression in zebrafish embryo nerve systems by using harmonic generation microscopy and morphant technology. J Biomed Opt. 2008;13:064041 pubmed publisher
    ..e., SHG microscopy and THG microscopy, successfully revealed the weak cell adhesion, cell apoptosis, nerve formation reduction, and neural tube distortion in the morphant zebrafish embryos. ..
  4. Guan B, Ma H, Wang Y, Hu Y, Lin Z, Zhu Z, et al. Vitreoscilla hemoglobin (VHb) overexpression increases hypoxia tolerance in zebrafish (Danio rerio). Mar Biotechnol (NY). 2011;13:336-44 pubmed publisher
    ..These results suggest that that vhb gene may be an efficient candidate for genetically modifying hypoxia tolerance in fish. ..
  5. Kopp R, Schwerte T, Egg M, Sandbichler A, Egger B, Pelster B. Chronic reduction in cardiac output induces hypoxic signaling in larval zebrafish even at a time when convective oxygen transport is not required. Physiol Genomics. 2010;42A:8-23 pubmed publisher
    ..The results showed that a chronic reduction in blood flow generated hypoxic molecular signals despite partial compensation by increased oxygen carrying capacity and transiently slowed the overall development of zebrafish bre larvae. ..
  6. Lim S, Esain V, Kwan W, Theodore L, Cortes M, Frost I, et al. HIF1?-induced PDGFR? signaling promotes developmental HSC production via IL-6 activation. Exp Hematol. 2017;46:83-95.e6 pubmed publisher
    ..Together, these findings define a Hif1?-regulated signaling axis mediated through PBFGB/PDGFR? and IL-6/IL-6R that acts to control embryonic HSPC production. ..
  7. Köblitz L, Fiechtner B, Baus K, Lussnig R, Pelster B. Developmental Expression and Hypoxic Induction of Hypoxia Inducible Transcription Factors in the Zebrafish. PLoS ONE. 2015;10:e0128938 pubmed publisher
    ..In these early developmental stages Hif-1α therefore appears to be more important for the coordination of hypoxic responsiveness. ..
  8. Robertson C, Wright P, Köblitz L, Bernier N. Hypoxia-inducible factor-1 mediates adaptive developmental plasticity of hypoxia tolerance in zebrafish, Danio rerio. Proc Biol Sci. 2014;281: pubmed publisher
    ..We conclude that mounting a HIF-1 response during embryogenesis is associated with long-term impacts on the phenotype of later stages which could influence both individual hypoxia tolerance and population dynamics. ..
  9. Egg M, Paulitsch M, Ennemoser Y, Wüstenhagen A, Schwerte T, Sandbichler A, et al. Chronodisruption increases cardiovascular risk in zebrafish via reduced clearance of senescent erythrocytes. Chronobiol Int. 2014;31:680-9 pubmed publisher
    ..The results might shed new light on the etiology of the increased cardiovascular risk observed among shiftworkers. ..
  10. Lo K, Hui M, Yu R, Wu R, Cheng S. Hypoxia impairs primordial germ cell migration in zebrafish (Danio rerio) embryos. PLoS ONE. 2011;6:e24540 pubmed publisher
    ..IGF signaling is shown to be one of the possible mechanisms for the causal link between hypoxia and PGC migration. We propose that hypoxia causes PGC migration defect by inhibiting IGF signaling through the induction of IGFBP-1. ..
  11. Hyvärinen J, Parikka M, Sormunen R, Ramet M, Tryggvason K, Kivirikko K, et al. Deficiency of a transmembrane prolyl 4-hydroxylase in the zebrafish leads to basement membrane defects and compromised kidney function. J Biol Chem. 2010;285:42023-32 pubmed publisher
    ..Many HIF target genes were induced in the P4H-TM-deficient morphants, but the observed phenotype is not likely to be mediated at least solely via the HIF pathway, and thus P4H-TM probably has additional, as yet unknown, substrates. ..
  12. Lien Y, Ou T, Lin Y, Kuo P, Lin H. Duplication and diversification of the spermidine/spermine N1-acetyltransferase 1 genes in zebrafish. PLoS ONE. 2013;8:e54017 pubmed publisher
  13. Priyadarshini M, Tuimala J, Chen Y, Panula P. A zebrafish model of PINK1 deficiency reveals key pathway dysfunction including HIF signaling. Neurobiol Dis. 2013;54:127-38 pubmed publisher
    ..Our findings suggest that a lack of pink1 in zebrafish alters many vital and critical pathways in addition to the HIF signaling pathway. ..
  14. Kuroyanagi J, Shimada Y, Zhang B, Ariyoshi M, Umemoto N, Nishimura Y, et al. Zinc finger MYND-type containing 8 promotes tumour angiogenesis via induction of vascular endothelial growth factor-A expression. FEBS Lett. 2014;588:3409-16 pubmed publisher
    ..Integrated analysis of human and zebrafish transcriptomes, which identified ZMYND8, might be a powerful strategy to determine also other molecular targets for inhibiting prostate cancer progression. ..
  15. Khatib A, Lahlil R, Hagedorn M, Delomenie C, Christophe O, Denis C, et al. Biological outcome and mapping of total factor cascades in response to HIF induction during regenerative angiogenesis. Oncotarget. 2016;7:12102-20 pubmed publisher
    ..Taken together, this study revealed the impact of HIF induction on regenerative angiogenesis and provided a framework to develop a gene network leading to regenerative process during HIF expression. ..
  16. So J, Kim J, Yoo K, Kim H, Jung S, Choi J, et al. FIH-1, a novel interactor of mindbomb, functions as an essential anti-angiogenic factor during zebrafish vascular development. PLoS ONE. 2014;9:e109517 pubmed publisher
    ..Taken together, our data suggest that FIH-1 interacts with Mib E3 Ubiquitin ligase and modulates vascular development by attenuating VEGF-A signaling activity. ..
  17. Rytkönen K, Prokkola J, Salonen V, Nikinmaa M. Transcriptional divergence of the duplicated hypoxia-inducible factor alpha genes in zebrafish. Gene. 2014;541:60-6 pubmed publisher
  18. Barriga E, Maxwell P, Reyes A, Mayor R. The hypoxia factor Hif-1? controls neural crest chemotaxis and epithelial to mesenchymal transition. J Cell Biol. 2013;201:759-76 pubmed publisher
    ..Our results point to Hif-1? as a novel and key regulator that integrates EMT and chemotaxis during migration of neural crest cells...
  19. Jopling C, Suñé G, Faucherre A, Fabregat C, Izpisua Belmonte J. Hypoxia induces myocardial regeneration in zebrafish. Circulation. 2012;126:3017-27 pubmed publisher
    ..These results indicate that hypoxia plays a positive role during heart regeneration, which should be taken into account in future strategies aimed at inducing heart regeneration in humans. ..
  20. Sánchez Garayzar A, Bahamonde P, Martyniuk C, Betancourt M, Munkittrick K. Hepatic gene expression profiling in zebrafish (Danio rerio) exposed to the fungicide chlorothalonil. Comp Biochem Physiol Part D Genomics Proteomics. 2016;19:102-111 pubmed publisher
    ..This study improves knowledge regarding whole animal exposures to chlorothalonil and identifies molecular signaling cascades that are sensitive to this fungicide in the fish liver. ..
  21. Martinovic D, Villeneuve D, Kahl M, Blake L, Brodin J, Ankley G. Hypoxia alters gene expression in the gonads of zebrafish (Danio rerio). Aquat Toxicol. 2009;95:258-72 pubmed publisher
    ..g., hydroxysteroid dehydrogenase alterations, downregulation of contractile elements, etc.). ..
  22. Lai Y, Lu Y, Lien H, Huang C, Hwang S. Foxa2 and Hif1ab regulate maturation of intestinal goblet cells by modulating agr2 expression in zebrafish embryos. Biochem J. 2016;473:2205-18 pubmed publisher
    ..Morpholino knockdown of foxa1 (forkhead box A1) reduced agr2 levels in the pharynx, whereas knockdown of foxa2 or hif1ab decreased intestinal agr2 expression and affected the differentiation and maturation of intestinal goblet cells...
  23. Kwong R, Kumai Y, Tzaneva V, Azzi E, Hochhold N, Robertson C, et al. Inhibition of calcium uptake during hypoxia in developing zebrafish is mediated by hypoxia-inducible factor. J Exp Biol. 2016;219:3988-3995 pubmed
    ..Overall, the current study revealed that hypoxic exposure inhibited Ca2+ uptake in developing zebrafish, probably owing to HIF-1?b-mediated suppression of ecac expression. ..
  24. Metelo A, Noonan H, Li X, Jin Y, Baker R, Kamentsky L, et al. Pharmacological HIF2α inhibition improves VHL disease-associated phenotypes in zebrafish model. J Clin Invest. 2015;125:1987-97 pubmed publisher
    ..This study demonstrates that small-molecule targeting of HIF2α improves VHL-related phenotypes in a vertebrate animal model and supports further exploration of this strategy for treating VHL disease. ..
  25. Binelli A, Del Giacco L, Santo N, Bini L, Magni S, Parolini M, et al. Carbon nanopowder acts as a Trojan-horse for benzo(α)pyrene in Danio rerio embryos. Nanotoxicology. 2017;11:371-381 pubmed publisher
    ..The entire dataset suggested a Trojan-horse mechanism involved in the biological impacts on Danio rerio embryos especially due to different bioaccumulation pathways and cellular targets. ..
  26. Nathan J, Lakshmanan G, Michael F, Seppan P, Ragunathan M. Expression of adenosine receptors and vegf during angiogenesis and its inhibition by pentoxifylline-A study using zebrafish model. Biomed Pharmacother. 2016;84:1406-1418 pubmed publisher
    ..Targeting the vegf signaling pathway with small molecules inhibiting adenosine receptors in addition to antagonizing vegf might be a promising approach to treat neovascular diseases of the retina and also tumors. ..
  27. Kuang X, Liu C, Fang J, Ma W, Zhang J, Cui S. The tumor suppressor gene lkb1 is essential for glucose homeostasis during zebrafish early development. FEBS Lett. 2016;590:2076-85 pubmed publisher
  28. Cheng F, Miao L, Wu Q, Gong X, Xiong J, Zhang J. Vinculin b deficiency causes epicardial hyperplasia and coronary vessel disorganization in zebrafish. Development. 2016;143:3522-3531 pubmed
    ..Together, our results reveal a previously unappreciated function of vinculin in epicardium and endocardium and reinforce the notion that well-balanced FAK activity is essential for coronary vessel development. ..
  29. Lister J, Capper A, Zeng Z, Mathers M, Richardson J, Paranthaman K, et al. A conditional zebrafish MITF mutation reveals MITF levels are critical for melanoma promotion vs. regression in vivo. J Invest Dermatol. 2014;134:133-140 pubmed publisher
    ..These studies are significant because they show that targeting MITF activity is a potent antitumor mechanism, but also show that caution is required because low levels of wild-type MITF activity are oncogenic. ..
  30. Cade L, Reyon D, Hwang W, Tsai S, Patel S, Khayter C, et al. Highly efficient generation of heritable zebrafish gene mutations using homo- and heterodimeric TALENs. Nucleic Acids Res. 2012;40:8001-10 pubmed publisher
    ..Our results suggest that construction of one to two heterodimeric TALEN pairs for any given gene will, in most cases, enable researchers to rapidly generate knockout zebrafish. ..
  31. Gerri C, Marín Juez R, Marass M, Marks A, Maischein H, Stainier D. Hif-1α regulates macrophage-endothelial interactions during blood vessel development in zebrafish. Nat Commun. 2017;8:15492 pubmed publisher
    ..Altogether, our data provide genetic evidence that Hif-1α regulates interactions between macrophages and endothelial cells starting with the mobilization of macrophages from the AGM. ..
  32. Griffitt R, Weil R, Hyndman K, Denslow N, Powers K, Taylor D, et al. Exposure to copper nanoparticles causes gill injury and acute lethality in zebrafish (Danio rerio). Environ Sci Technol. 2007;41:8178-86 pubmed
  33. Liu S, Zhu K, Chen N, Wang W, Wang H. Identification of HIF-1? promoter and expression regulation of HIF-1? gene by LPS and hypoxia in zebrafish. Fish Physiol Biochem. 2013;39:1153-63 pubmed publisher
    ..This synergistic effect was closely related to the living environment of fish, indicating that this mechanism would be more conducive to fish survival. ..
  34. Robertson A, Holmes G, Bojarczuk A, Burgon J, Loynes C, Chimen M, et al. A zebrafish compound screen reveals modulation of neutrophil reverse migration as an anti-inflammatory mechanism. Sci Transl Med. 2014;6:225ra29 pubmed publisher
  35. Ton C, Stamatiou D, Dzau V, Liew C. Construction of a zebrafish cDNA microarray: gene expression profiling of the zebrafish during development. Biochem Biophys Res Commun. 2002;296:1134-42 pubmed
    ..Our study provides the first utilization of cDNA microarray in the zebrafish and reveals dynamic changes in levels of gene expression in relation to development and survival of the zebrafish embryos under hypoxic stress. ..
  36. Huang C, Chen N, Wu X, He Y, Huang C, Liu H, et al. Zebrafish let-7b acts downstream of hypoxia-inducible factor-1? to assist in hypoxia-mediated cell proliferation and cell cycle regulation. Life Sci. 2017;171:21-29 pubmed publisher
    ..We also identified 4 novel potential HIF-1?-regulated miRNAs in zebrafish. ..
  37. Ma J, Evrard S, Badiola I, Siegfried G, Khatib A. Regulation of the proprotein convertases expression and activity during regenerative angiogenesis: Role of hypoxia-inducible factor (HIF). Eur J Cell Biol. 2017;96:457-468 pubmed publisher
  38. Tan T, Yu R, Wu R, Kong R. Overexpression and Knockdown of Hypoxia-Inducible Factor 1 Disrupt the Expression of Steroidogenic Enzyme Genes and Early Embryonic Development in Zebrafish. Gene Regul Syst Bio. 2017;11:1177625017713193 pubmed publisher
    ..Overall, the findings from this study indicate that HIF-1-mediated mechanisms are likely involved in the regulation of specific steroidogenic genes. ..
  39. de Bruin A, A Cornelissen P, Kirchmaier B, Mokry M, Iich E, Nirmala E, et al. Genome-wide analysis reveals NRP1 as a direct HIF1?-E2F7 target in the regulation of motorneuron guidance in vivo. Nucleic Acids Res. 2016;44:3549-66 pubmed publisher
    ..Therefore, we conclude that repression of NRP1 by the HIF1?-E2F7 complex regulates MN axon guidance in vivo. ..
  40. Chu D, Li V, Yu R. Leptin: clue to poor appetite in oxygen-starved fish. Mol Cell Endocrinol. 2010;319:143-6 pubmed publisher
    ..This is the first report to show that leptin gene expression in fish is regulated by hypoxia possibly via the involvement of HIF-1. ..
  41. Pelster B, Egg M. Multiplicity of hypoxia-inducible transcription factors and their connection to the circadian clock in the zebrafish. Physiol Biochem Zool. 2015;88:146-57 pubmed publisher
  42. Zhao Y, Huang X, Ding T, Gong Z. Enhanced angiogenesis, hypoxia and neutrophil recruitment during Myc-induced liver tumorigenesis in zebrafish. Sci Rep. 2016;6:31952 pubmed publisher
    ..In sum, the current study demonstrated that the Myc-induced liver tumor model in zebrafish provides an excellent platform for study of tumor microenvironment. ..
  43. Zhang P, Lu L, Yao Q, Li Y, Zhou J, Liu Y, et al. Molecular, functional, and gene expression analysis of zebrafish hypoxia-inducible factor-3?. Am J Physiol Regul Integr Comp Physiol. 2012;303:R1165-74 pubmed publisher
    ..These results provide new information about the structural and functional conservation, spatial and temporal expression, and physiological regulation of hif-3? in a teleost model organism. ..
  44. Gray C, Packham I, Wurmser F, Eastley N, Hellewell P, Ingham P, et al. Ischemia is not required for arteriogenesis in zebrafish embryos. Arterioscler Thromb Vasc Biol. 2007;27:2135-41 pubmed
    ..We conclude that NO and myeloid cell-dependent collateral vessel development is an evolutionarily ancient response to arterial occlusion and is able to proceed in the absence of ischemia. ..
  45. Xu T, Zhao J, Hu P, Dong Z, Li J, Zhang H, et al. Pentachlorophenol exposure causes Warburg-like effects in zebrafish embryos at gastrulation stage. Toxicol Appl Pharmacol. 2014;277:183-91 pubmed publisher
    ..Taken together, our results demonstrated that PCP causes a Warburg-like effect on zebrafish embryos during gastrulation, and the affected embryos had the phenotype of developmental delay...
  46. Egg M, Köblitz L, Hirayama J, Schwerte T, Folterbauer C, Kurz A, et al. Linking oxygen to time: the bidirectional interaction between the hypoxic signaling pathway and the circadian clock. Chronobiol Int. 2013;30:510-29 pubmed publisher
  47. Vettori A, Greenald D, Wilson G, Peron M, Facchinello N, Markham E, et al. Glucocorticoids promote Von Hippel Lindau degradation and Hif-1? stabilization. Proc Natl Acad Sci U S A. 2017;114:9948-9953 pubmed publisher
    ..Our data support a model for GCs to stabilize HIF through activation of c-src and subsequent destabilization of pVHL. ..
  48. Stevenson T, Trinh T, Kogelschatz C, Fujimoto E, Lush M, Piotrowski T, et al. Hypoxia disruption of vertebrate CNS pathfinding through ephrinB2 Is rescued by magnesium. PLoS Genet. 2012;8:e1002638 pubmed publisher
    ..These results demonstrate that evolutionarily conserved genetic pathways regulate connectivity changes in the CNS in response to hypoxia, and they support a potential neuroprotective role for magnesium. ..
  49. Huang C, Chen N, Wu X, Huang C, He Y, Tang R, et al. The zebrafish miR-462/miR-731 cluster is induced under hypoxic stress via hypoxia-inducible factor 1α and functions in cellular adaptations. FASEB J. 2015;29:4901-13 pubmed publisher
  50. Bestman J, Stackley K, Rahn J, Williamson T, Chan S. The cellular and molecular progression of mitochondrial dysfunction induced by 2,4-dinitrophenol in developing zebrafish embryos. Differentiation. 2015;89:51-69 pubmed publisher
  51. Almeida D, Bianchini A, Marins L. Growth hormone overexpression generates an unfavorable phenotype in juvenile transgenic zebrafish under hypoxic conditions. Gen Comp Endocrinol. 2013;194:102-9 pubmed publisher
    ..between transgenesis and hypoxia caused an increased expression of hemoglobin (Hb), hypoxia-inducible factor (HIF1a) and prolyl-4-hydroxylase (PHD) genes...