PUBLICATION
Hypoxia-inducible factor 3 is an oxygen-dependent transcription activator and regulates a distinct transcriptional response to hypoxia
- Authors
- Zhang, P., Yao, Q., Lu, L., Li, Y., Chen, P.J., Duan, C.
- ID
- ZDB-PUB-140513-380
- Date
- 2014
- Source
- Cell Reports 6: 1110-21 (Journal)
- Registered Authors
- Duan, Cunming
- Keywords
- none
- Datasets
- GEO:GSE54318
- MeSH Terms
-
- Animals
- Basic Helix-Loop-Helix Transcription Factors/genetics
- Basic Helix-Loop-Helix Transcription Factors/metabolism*
- Cell Hypoxia/genetics
- Cell Hypoxia/physiology*
- Cell Line, Tumor
- Gene Expression Regulation
- HEK293 Cells
- Humans
- Promoter Regions, Genetic
- Transcription, Genetic
- Transcriptional Activation
- Zebrafish
- PubMed
- 24613356 Full text @ Cell Rep.
Citation
Zhang, P., Yao, Q., Lu, L., Li, Y., Chen, P.J., Duan, C. (2014) Hypoxia-inducible factor 3 is an oxygen-dependent transcription activator and regulates a distinct transcriptional response to hypoxia. Cell Reports. 6:1110-21.
Abstract
Hypoxia-inducible factors (HIFs) play key roles in the cellular response to hypoxia. It is widely accepted that whereas HIF-1 and HIF-2 function as transcriptional activators, HIF-3 inhibits HIF-1/2α action. Contrary to this idea, we show that zebrafish Hif-3α has strong transactivation activity. Hif-3α is degraded under normoxia. Mutation of P393, P493, and L503 inhibits this oxygen-dependent degradation. Transcriptomics and chromatin immunoprecipitation analyses identify genes that are regulated by Hif-3α, Hif-1α, or both. Under hypoxia or when overexpressed, Hif-3α binds to its target gene promoters and upregulates their expression. Dominant-negative inhibition and knockdown of Hif-3α abolish hypoxia-induced Hif-3α-promoter binding and gene expression. Hif-3α not only mediates hypoxia-induced growth and developmental retardation but also possesses hypoxia-independent activities. Importantly, transactivation activity is conserved and human HIF-3α upregulates similar genes in human cells. These findings suggest that Hif-3 is an oxygen-dependent transcription factor and activates a distinct transcriptional response to hypoxia.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping