title: Sequence and functional characterization of hypoxia-inducible factors, HIF1α, HIF2αa, and HIF3α, from the estuarine fish,Fundulus heteroclitus.
abstract: The hypoxia-inducible factor (HIF) family of transcription factors plays central roles in the development, physiology, pathology, and environmental adaptation of animals. Because many aquatic habitats are characterized by episodes of low dissolved oxygen, fish represent ideal models to study the roles of HIF in the response to aquatic hypoxia. The estuarine fishFundulus heteroclitusis found in habitats prone to hypoxia. It responds to low oxygen via behavioral, physiological, and molecular changes, and one member of the HIF family, HIF2α, has been previously described. Herein, cDNA sequencing, phylogenetic analyses, and genomic approaches were used to determine other members of the HIFα family fromF. heteroclitusand their relationships to HIFα subunits from other vertebrates. In vitro and cellular approaches demonstrated that full-length forms of HIF1α, HIF2α, and HIF3α independently formed complexes with the β-subunit, aryl hydrocarbon receptor nuclear translocator, to bind to hypoxia response elements and activate reporter gene expression. Quantitative PCR showed that HIFα mRNA abundance varied among organs of normoxic fish in an isoform-specific fashion. Analysis of theF. heteroclitusgenome revealed a locus encoding a second HIF2α-HIF2αb-a predicted protein lacking oxygen sensing and transactivation domains. Finally, sequence analyses demonstrated polymorphism in the coding sequence of eachF. heteroclitusHIFα subunit, suggesting that genetic variation in these transcription factors may play a role in the variation in hypoxia responses among individuals or populations.
authors.affiliation: Department of Biological Sciences, University of New Orleans, New Orleans, Louisiana.|College of Pharmacy, Xavier University of New Orleans, New Orleans, Louisiana; and.
authors.forename: Ian K
authors.initials: IK
authors.lastname: Townley
authors.affiliation: Biology Department, Woods Hole Oceanographic Institution, Woods Hole, Massachusetts.
authors.forename: Sibel I
authors.initials: SI
authors.lastname: Karchner
authors.affiliation: Department of Biological Sciences, University of New Orleans, New Orleans, Louisiana.|College of Pharmacy, Xavier University of New Orleans, New Orleans, Louisiana; and.
authors.forename: Elena
authors.initials: E
authors.lastname: Skripnikova
authors.affiliation: College of Pharmacy, Xavier University of New Orleans, New Orleans, Louisiana; and.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Wiese
authors.affiliation: Biology Department, Woods Hole Oceanographic Institution, Woods Hole, Massachusetts.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Hahn
authors.affiliation: Department of Biological Sciences, University of New Orleans, New Orleans, Louisiana brees@uno.edu.
authors.forename: Bernard B
authors.initials: BB
authors.lastname: Rees
mesh_terms: D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D063366:Estuaries; D023781:Fundulidae / Q000145:classification / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D013045:Species Specificity; D013329:Structure-Activity Relationship
chemical_list: D051792:Basic Helix-Loop-Helix Proteins
keywords: environmental adaptation; gene expression; oxygen