Abstract
The ubiquitously expressed hypoxia-inducible factor-1α (HIF-1α) acts as a key transcription factor in regulating metabolism, development, cellular survival, proliferation and pathology under hypoxia condition. Compared to mammals, fish are more vulnerable to hypoxia stress and contamination; however, the regulation of HIF-1α in fish remains obscure. In this study, zebrafish HIF-1α promoter was cloned and found to possess a CpG island located at −97 to +403, but the canonical TATA-box was absent. Aligning 240-bp HIF-1α proximal promoter region of zebrafish with other vertebrates showed more than 82 % identity with cyprinid fishes. Further luciferase analysis suggested that the minimal core promoter might locate at −134 to +97, and several putative transcription factor binding sites were found in this region by bioinformatic analysis. Moreover, it was shown that the zebrafish HIF-1α mRNA was significantly activated by 10 μg/mL lipopolysaccharide (LPS) under hypoxia condition and peaked at 8 h after treatment, suggesting LPS- and hypoxia-regulated zebrafish HIF-1α transcriptional activity in a synergistic pattern. This synergistic effect was closely related to the living environment of fish, indicating that this mechanism would be more conducive to fish survival.
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References
Akira S, Uematsu S, Takeuchi O (2006) Pathogen recognition and innate immunity. Cell 124:783–801
Belaiba RS, Bonello S, Zähringer C, Schmidt S, Hess J, Kietzmann T, Görlach A (2007) Hypoxia up-regulates hypoxia-inducible factor-1alpha transcription by involving phosphatidylinositol 3-kinase and nuclear factor kappaB in pulmonary artery smooth muscle cells. Mol Biol Cell 18:4691–4697
Blouin CC, Pagé EL, Soucy GM, Richard DE (2004) Hypoxic gene activation by lipopolysaccharide in macrophages: implication of hypoxia-inducible factor 1 alpha. Blood 103:1124–1130
Chen R, Liliental JE, Kowalski PE, Lu Q, Cohen SN (2011) Regulation of transcription of hypoxia-inducible factor-1 alpha (HIF-1 alpha) by heat shock factors HSF2 and HSF4. Oncogene 30:2570–2580
Chen N, Chen LP, Zhang J, Chen C, Wei XL, Gul Y, Wang WM, Wang HL (2012) Molecular characterization and expression analysis of three hypoxia-inducible factor alpha subunits, HIF-1alpha/2alpha/3alpha of the hypoxia-sensitive freshwater species, Chinese sucker. Gene 498:81–90
Connell DW, Lam P, Richardson B, Wu R (1999) Introduction to Ecotoxicology. Blackwell, Oxford
Frede S, Stockmann C, Freitag P, Fandrey J (2006) Bacterial lipopolysaccharide induces HIF-1 activation in human monocytes via p44/42 MAPK and NF-kappa B. Biochem J 396:517–527
Imtiyaz HZ, Simon MC (2010) Hypoxia-Inducible factors as essential regulators of inflammation. Curr Top Microbiol Immunol 345:105–120
Ivan M, Kondo K, Yang H, Kim W, Valiando J, Ohh M, Salic A, Asara JM, Lane WS, Kaelin WG Jr (2001) HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing. Science 292:464–468
Iyer NV, Leung SW, Semenza GL (1998) The human hypoxia-inducible factor 1alpha gene: HIF1A structure and evolutionary conservation. Genomics 52:159–165
Kajimura S, Aida K, Duan C (2005) Insulin-like growth factor-binding protein-1 (IGFBP-1) mediates hypoxia-induced embryonic growth and developmental retardation. Proc Natl Acad Sci USA 102:1240–1245
Kim HY, Kim YH, Nam BH, Kong HJ, Kim HH, Kim YJ, An WG, Cheong J (2007) HIF-1 alpha expression in response to lipopolysaccharide mediates induction of hepatic inflammatory cytokine TNF alpha. Exp Cell Res 313:1866–1876
Kopp R, Köblitz L, Egg M, Pelster B (2011) HIF signaling and overall gene expression changes during hypoxia and prolonged exercise differ considerably. Physiol Genomics 43:506–516
Koshikawa N, Hayashi J, Nakagawara A, Takenaga K (2009) Reactive oxygen species-generating mitochondrial DNA mutation up-regulates hypoxia-inducible factor-1alpha gene transcription via phosphatidylinositol 3-kinase-Akt/protein kinase C/histone deacetylase pathway. J Biol Chem 284:33185–33194
Law S, Wu R, Ng P, Yu R, Kong R (2006) Cloning and expression analysis of two distinct HIF-alpha isoforms–gcHIF-1alpha and gcHIF-4alpha–from the hypoxia-tolerant grass carp, Ctenopharyngodon idellus. BMC Mol Biol 7:15. doi:10.1186/1471-2199-7-15
Marzec M, Liu X, Wong W, Yang Y, Pasha T, Kantekure K, Zhang P, Woetmann A, Cheng M, Odum N, Wasik MA (2010) Oncogenic kinase NPM/ALK induces expression of HIF1α mRNA. Oncogene 30:1372–1378
Mayr B, Montminy M (2001) Transcriptional regulation by the phosphorylation-dependent factor CREB. Nat Rev Mol Cell Biol 2:599–609
Mi Z, Rapisarda A, Taylor L, Brooks A, Creighton-Gutteridge M, Melillo G, Varesio L (2008) Synergistic induction of HIF-1alpha transcriptional activity by hypoxia and lipopolysaccharide in macrophages. Cell Cycle 7:232–241
Minet E, Ernest I, Michel G, Roland I, Remacle J, Raes M, Michiels C (1999) HIF1A gene transcription is dependent on a core promoter sequence encompassing activating and inhibiting sequences located upstream from the transcription initiation site and cis elements located within the 5′UTR. Biochem Biophys Res Commun 261:534–540
Mole DR, Blancher C, Copley RR, Pollard PJ, Gleadle JM, Ragoussis J, Ratcliffe PJ (2009) Genome-wide association of hypoxia-inducible factor (HIF)-1α and HIF-2α DNA binding with expression profiling of hypoxia-inducible transcripts. J Biol Chem 284:16767–16775
Nikinmaa M, Rees BB (2005) Oxygen-dependent gene expression in fishes. Am J Physiol Regul Integr Comp Physiol 288:R1079–R1090
Nourbakhsh M, Hauser H (1999) Constitutive silencing of IFN-β promoter is mediated by NRF (NF-κB-repressing factor), a nuclear inhibitor of NF-κB. EMBO J 18(22):6415–6425
Novoa B, Bowman TV, Zon L, Figueras A (2009) LPS response and tolerance in the zebrafish (Danio rerio). Fish Shellfish Immunol 26:326–331
Oh YT, Lee JY, Yoon H, Lee EH, Baik HH, Kim SS, Ha J, Yoon KS, Choe W, Kang I (2008) Lipopolysaccharide induces hypoxia-inducible factor-1 alpha mRNA expression and activation via NADPH oxidase and Sp1-dependent pathway in BV2 murine microglial cells. Neurosci Lett 431:155–160
Rahman MS, Thomas P (2007) Molecular cloning, characterization and expression of two hypoxia-inducible factor alpha subunits, HIF-1alpha and HIF-2alpha, in a hypoxia-tolerant marine teleost, Atlantic croaker (Micropogonias undulatus). Gene 396(2):273–282
Renshaw SA, Trede NS (2012) A model 450 million years in the making: zebrafish and vertebrate immunity. Dis Models Mech 5(1):38–47
Rimoldi S, Terova G, Ceccuzzi P, Marelli S, Antonini M, Saroglia M (2012) HIF-1alpha mRNA levels in Eurasian perch (Perca fluviatilis) exposed to acute and chronic hypoxia. Mol Biol Rep 39(4):4009–4015
Rissanen E, Tranberg HK, Sollid J, Nilsson GE, Nikinmaa M (2006) Temperature regulates hypoxia-inducible factor-1 (HIF-1) in a poikilothermic vertebrate, crucian carp (Carassius carassius). J Exp Biol 209:994–1003
Rius J, Guma M, Schachtrup C, Akassoglou K, Zinkernagel AS, Nizet V, Johnson RS, Haddad GG, Karin M (2008) NF-kappaB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1alpha. Nature 453:807–811
Rojas DA, Perez-Munizaga DA, Centanin L, Antonelli M, Wappner P, Allende ML, Reyes AE (2007) Cloning of hif-1α and hif-2α and mRNA expression pattern during development in zebrafish. Gene Expr Patterns 7:339–345
Rytkönen KT, Vuori KA, Primmer CR, Nikinmaa M (2007) Comparison of hypoxia-inducible factor-1 alpha in hypoxia-sensitive and hypoxia-tolerant fish species. Comparative biochemistry and physiology part D. Genomics Proteomics 2(2):177–186
Scharte M, Han X, Uchiyama T, Tawadrous Z, Delude RL, Fink MP (2006) LPS increases hepatic HIF-1alpha protein and expression of the HIF-1-dependent gene aldolase A in rats. J Surg Res 135(2):262–267
Schödel J, Oikonomopoulos S, Ragoussis J, Pugh CW, Ratcliffe PJ, Mole DR (2011) High-resolution genome-wide mapping of HIF-binding sites by ChIP-seq. Blood 117:e207–e217
Schofield CJ, Ratcliffe PJ (2004) Oxygen sensing by HIF hydroxylases. Nat Rev Mol Cell Biol 5:343–354
Semenza GL (2003) Targeting HIF-1 for cancer therapy. Nat Rev Cancer 3:721–732
Semenza GL, Wang GL (1992) A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation. Mol Cell Biol 12:5447–5454
Semenza GL, Jiang BH, Leung SW, Passantino R, Concordet JP, Maire P, Giallongo A (1996) Hypoxia response elements in the aldolase A, enolase 1, and lactate dehydrogenase A gene promoters contain essential binding sites for hypoxia-inducible factor 1. J Biol Chem 271:32529–32537
Sepulcre MP, Alcaraz-Pérez F, López-Muñoz A, Roca FJ, Meseguer J, Cayuela ML, Mulero V (2009) Evolution of lipopolysaccharide (LPS) recognition and signaling: fish TLR4 does not recognize LPS and negatively regulates NF-kappaB activation. J Immunol 182:1836–1845
Shen RJ, Jiang XY, Pu JW, Zou SM (2010) HIF-1alpha and -2alpha genes in a hypoxia-sensitive teleost species Megalobrama amblycephala: cDNA cloning, expression and different responses to hypoxia. Comp Biochem Physiol B: Biochem Mol Biol 157:273–280
Sipe CW, Gruber EJ, Saha MS (2004) Short upstream region drives dynamic expression of hypoxia-inducible factor 1alpha during Xenopus development. Dev Dyn 230:229–238
Soitamo AJ, Rabergh CM, Gassmann M, Sistonen L, Nikinmaa M (2001) Characterization of a hypoxia-inducible factor (HIF-1alpha) from rainbow trout. Accumulation of protein occurs at normal venous oxygen tension. J Biol Chem 276:19699–19705
Tang R, Dodd A, Lai D, McNabb WC, Love DR (2007) Validation of zebrafish (Danio rerio) reference genes for quantitative real-time RT-PCR normalization. Acta Biochim Biophys Sin 39(5):384–390
Terova G, Rimoldi S, Corà S, Bernardini G, Gornati R, Saroglia M (2008) Acute and chronic hypoxia affects HIF-1α mRNA levels in sea bass (Dicentrarchus labrax). Aquaculture 279(1):150–159
Trede NS, Zapata A, Zon LI (2001) Fishing for lymphoid genes. Trends Immunol 22:302–307
Van Uden P, Kenneth NS, Rocha S (2008) Regulation of hypoxia-inducible factor-1α by NF-κB. Biochem J 412:477–484
Watzke J, Schirmer K, Scholz S (2007) Bacterial lipopolysaccharides induce genes involved in the innate immune response in embryos of the zebrafish (Danio rerio). Fish Shellfish Immunol 23(4):901–905
Wenger RH, Rolfs A, Kvietikova I, Spielmann P, Zimmermann DR, Gassmann M (1997) The mouse gene for hypoxia-inducible factor-1alpha–genomic organization, expression and characterization of an alternative first exon and 5′ flanking sequence. Eur J Biochem 246:155–165
Wenger RH, Stiehl DP, Camenisch G (2005) Integration of oxygen signaling at the consensus HRE. Sci STKE 2005:re12
Westerfield M (2000) The Zebrafish Book: a guide for the laboratory use of zebrafish (Danio rerio). University of Oregon Press, Eugene, OR
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The research was supported by the natural science foundation of China (30901099), program for new century excellent talents in university (NCET-10-0403) and the fundamental research funds for the central universities (2011PY072, 2010PY004).
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Liu, S., Zhu, K., Chen, N. et al. Identification of HIF-1α promoter and expression regulation of HIF-1α gene by LPS and hypoxia in zebrafish. Fish Physiol Biochem 39, 1153–1163 (2013). https://doi.org/10.1007/s10695-013-9771-0
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DOI: https://doi.org/10.1007/s10695-013-9771-0