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    Sequence and functional characterization of hypoxia inducible factors, HIF1α, HIF2αa, and HIF3α, from the estuarine fish, Fundulus heteroclitus

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    Townley et al 2016 Author's Accepted Ms.pdf (7.377Mb)
    Date
    2016-11
    Author
    Townley, Ian K.  Concept link
    Karchner, Sibel I.  Concept link
    Skripnikova, Elena  Concept link
    Wiese, Thomas E.  Concept link
    Hahn, Mark E.  Concept link
    Rees, Bernard B.  Concept link
    Metadata
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    Citable URI
    https://hdl.handle.net/1912/8935
    As published
    https://doi.org/10.1152/ajpregu.00402.2016
    Keyword
     Environmental adaptation; Oxygen; Gene expression 
    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 fish Fundulus heteroclitus occurs 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 from F. heteroclitus and their relationships to HIFα subunits from other vertebrates. In vitro and cellular approaches demonstrated that full-length forms of HIF1α, 2α, and 3α independently formed complexes with the β subunit (ARNT) 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 the F. heteroclitus genome 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 each F. heteroclitus HIFα subunit, suggesting that genetic variation in these transcription factors may play a role in the variation in hypoxia responses among individuals or populations.
    Description
    Author Posting. © The Author(s), 2016. This is the author's version of the work. It is posted here under a nonexclusive, irrevocable, paid-up, worldwide license granted to WHOI. It is made available for personal use, not for redistribution. The definitive version was published in American Journal of Physiology-Regulatory Integrative and Comparative Physiology, 312 (2017): R412-R425, doi:10.1152/ajpregu.00402.2016.
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    Suggested Citation
    Preprint: Townley, Ian K., Karchner, Sibel I., Skripnikova, Elena, Wiese, Thomas E., Hahn, Mark E., Rees, Bernard B., "Sequence and functional characterization of hypoxia inducible factors, HIF1α, HIF2αa, and HIF3α, from the estuarine fish, Fundulus heteroclitus", 2016-11, https://doi.org/10.1152/ajpregu.00402.2016, https://hdl.handle.net/1912/8935
     
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