Back to Search
Start Over
Inherent DNA-binding specificities of the HIF-1α and HIF-2α transcription factors in chromatin.
- Source :
-
EMBO reports [EMBO Rep] 2019 Jan; Vol. 20 (1). Date of Electronic Publication: 2018 Nov 14. - Publication Year :
- 2019
-
Abstract
- Hypoxia-inducible factor (HIF) is the major transcriptional regulator of cellular responses to hypoxia. The two principal HIF-α isoforms, HIF-1α and HIF-2α, are progressively stabilized in response to hypoxia and form heterodimers with HIF-1β to activate a broad range of transcriptional responses. Here, we report on the pan-genomic distribution of isoform-specific HIF binding in response to hypoxia of varying severity and duration, and in response to genetic ablation of each HIF-α isoform. Our findings reveal that, despite an identical consensus recognition sequence in DNA, each HIF heterodimer loads progressively at a distinct repertoire of cell-type-specific sites across the genome, with little evidence of redistribution under any of the conditions examined. Marked biases towards promoter-proximal binding of HIF-1 and promoter-distant binding of HIF-2 were observed under all conditions and were consistent in multiple cell type. The findings imply that each HIF isoform has an inherent property that determines its binding distribution across the genome, which might be exploited to therapeutically target the specific transcriptional output of each isoform independently.<br /> (© 2018 The Authors. Published under the terms of the CC BY 4.0 license.)
- Subjects :
- Cell Line
Chromatin genetics
DNA genetics
DNA-Binding Proteins genetics
Epigenomics
Gene Expression Regulation genetics
Humans
Promoter Regions, Genetic
Protein Isoforms genetics
Basic Helix-Loop-Helix Transcription Factors genetics
Cell Hypoxia genetics
Hypoxia-Inducible Factor 1, alpha Subunit genetics
Transcription, Genetic
Subjects
Details
- Language :
- English
- ISSN :
- 1469-3178
- Volume :
- 20
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- EMBO reports
- Publication Type :
- Academic Journal
- Accession number :
- 30429208
- Full Text :
- https://doi.org/10.15252/embr.201846401