Publication Date:
2022-05-25
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.
Description:
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:
This research was supported in
part by the National Science Foundation (IBN-0236494 and DEB-1120263) and by National
Institute of Environmental Health Sciences (NIEHS) grant P42ES007381 (Superfund Basic
Research Program at Boston University). Data interpretation was aided by reference to a
preliminary draft of the F. heteroclitus genome sequence, which was supported by funding from
the National Science Foundation (collaborative research grants DEB-1120512, DEB-1265282,
DEB-1120013, DEB-1120263, DEB-1120333, DEB-1120398).
Keywords:
Environmental adaptation
;
Oxygen
;
Gene expression
Repository Name:
Woods Hole Open Access Server
Type:
Preprint
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