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Accession: PRJNA701449 ID: 701449

A functional map of genomic HIF1α-DNA complexes in the eye lens revealed through multiomics analysis [RNA-seq] (chicken)

See Genome Information for Gallus gallus
Background: During eye lens development the fetal vasculature regresses leaving the lens without a direct oxygen source. Both embryonically and throughout adult life, the lens contains a decreasing oxygen gradient from the surface to the core that parallels the natural differentiation of immature surface epithelial cells into mature core transparent fiber cells. These properties of the lens suggest a potential role for hypoxia in the regulation of genes required for mature lens structure and function. Since HIF1α is a master regulator of the hypoxic response, these lens properties also implicate HIF1α as a potential requirement for lens formation and homeostasis. Here, we employed a multiomics approach combining CUT&RUN, RNAseq and ATACseq analysis to establish the genomic complement of lens HIF1α binding sites, genes activated or repressed by HIF1α and the chromatin states of HIF1α-regulated genes. Results: CUT&RUN analysis revealed 8,375 HIF1α-DNA binding complexes in the chick lens genome. 1,190 HIF1α-DNA binding complexes were significantly clustered within chromatin accessible regions (χ2 test p < 1x10-55) identified by ATACseq. Formation of the identified HIF1α-DNA complexes paralleled the activation or repression of 526 genes, 116 of which contained HIF1α binding sites within 10kB of the transcription start sites. Some of the identified HIF1α genes have previously established lens functions while others have novel functions never before examined in the lens. GO and pathway analysis of these genes implicate HIF1α in the control of a wide-variety of cellular pathways potentially critical for lens formation, structure and function including glycolysis, cell cycle regulation, chromatin remodeling, Notch and Wnt signaling, differentiation, development, and transparency. Conclusions: These data establish the first functional map of genomic HIF1α-DNA complexes in the eye lens. They identify HIF1α as an important regulator of a wide-variety of genes previously shown to be critical for lens formation and function and they reveal a requirement for HIF1α in the regulation of a wide-variety of genes not yet examined for lens function. They support a requirement for HIF1α in lens development, structure and function and they provide a basis for understanding the potential roles and requirements for HIF1α in the development, structure and function of more complex tissues. Overall design: RNA-seq of six samples
AccessionPRJNA701449; GEO: GSE166632
Data TypeTranscriptome or Gene expression
ScopeMultiisolate
OrganismGallus gallus[Taxonomy ID: 9031]
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda; Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae; Phasianinae; Gallus; Gallus gallus
PublicationsDisatham J et al., "A functional map of genomic HIF1α-DNA complexes in the eye lens revealed through multiomics analysis.", BMC Genomics, 2021 Jul 3;22(1):497
Grants
  • "Hypoxia Regulation of the Lens" (Grant ID R01 EY029708, National Eye Institute)
SubmissionRegistration date: 11-Feb-2021
Florida Atlantic University
RelevanceAgricultural
Project Data:
Resource NameNumber
of Links
Sequence data
SRA Experiments6
Publications
PubMed1
PMC1
Other datasets
BioSample6
GEO DataSets1
GEO Data Details
ParameterValue
Data volume, Supplementary Mbytes1
SRA Data Details
ParameterValue
Data volume, Gbases42
Data volume, Mbytes13282

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