ZFIN ID: ZDB-PUB-060224-1
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
Kajimura, S., Aida, K., and Duan, C.
Date: 2006
Source: Molecular and cellular biology   26 (3): 1142-1155 (Journal)
Registered Authors: Duan, Cunming
Keywords: none
MeSH Terms:
  • Animals
  • Consensus Sequence
  • Embryo, Nonmammalian/metabolism
  • Embryonic Development/genetics
  • Gene Expression Regulation, Developmental*
  • Hypoxia/genetics*
  • Hypoxia-Inducible Factor 1/metabolism*
  • Insulin-Like Growth Factor Binding Protein 1/genetics*
  • Mutation
  • Promoter Regions, Genetic
  • Response Elements
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish Proteins/genetics*
PubMed: 16428465 Full text @ Mol. Cell. Biol.
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.