PUBLICATION
Understanding hypoxia-induced gene expression in early development: in vitro and in vivo analysis of hypoxia-inducible factor 1-regulated zebra fish insulin-like growth factor binding protein 1 gene expression
- Authors
- Kajimura, S., Aida, K., and Duan, C.
- ID
- ZDB-PUB-060224-1
- Date
- 2006
- Source
- Molecular and cellular biology 26 (3): 1142-1155 (Journal)
- Registered Authors
- Duan, Cunming
- Keywords
- none
- MeSH Terms
-
- Hypoxia/genetics*
- Promoter Regions, Genetic
- Embryo, Nonmammalian/metabolism
- Insulin-Like Growth Factor Binding Protein 1/genetics*
- Hypoxia-Inducible Factor 1/metabolism*
- Embryonic Development/genetics
- Mutation
- Zebrafish/embryology*
- Zebrafish/genetics
- Gene Expression Regulation, Developmental*
- Animals
- Response Elements
- Consensus Sequence
- Zebrafish Proteins/genetics*
- PubMed
- 16428465 Full text @ Mol. Cell. Biol.
Citation
Kajimura, S., Aida, K., and Duan, C. (2006) Understanding hypoxia-induced gene expression in early development: in vitro and in vivo analysis of hypoxia-inducible factor 1-regulated zebra fish insulin-like growth factor binding protein 1 gene expression. Molecular and cellular biology. 26 (3):1142-1155.
Abstract
Insulin-like growth factor binding protein 1 (IGFBP-1) is a hypoxia-inducible gene that plays an important role in regulating embryonic growth and development under hypoxic stress. The molecular mechanisms underlying hypoxia-induced IGFBP-1 gene expression in the embryonic tissues are not well understood. Here we report that the hypoxia-inducible factor 1 (HIF-1) pathway is established in early embryogenesis and mediates hypoxia-induced IGFBP-1 expression. Hypoxia increased the HIF-1 activity, and HIF-1alpha overexpression or CoCl2 treatment resulted in elevated IGFBP-1 expression in zebra fish embryos. Although the zebra fish IGFBP-1 promoter contains 13 consensus hypoxia response elements (HREs), deletion and mutational analysis revealed that only the HRE positioned at -1090/-1086 is required for the hypoxia and HIF-1 induction. Further experiments revealed that there is an HIF-1 ancillary sequence (HAS) adjacent only to the functional HRE. Mutation of this HAS greatly reduced the responsiveness of the IGFBP-1 promoter to hypoxia and HIF-1. The HAS does not directly bind to HIF-1 or affect the binding of the HRE to HIF-1. The HAS is bound to a nuclear protein(s), and this HAS binding activity is reduced by hypoxia. These results suggest that HIF-1 mediates hypoxia-induced IGFBP-1 gene expression in early development by selectively interacting with the -1090/-1086 HRE and its adjacent HAS.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping