Preferential binding of HIF-1 to transcriptionally active loci determines cell-type specific response to hypoxia

Genome Biol. 2009;10(10):R113. doi: 10.1186/gb-2009-10-10-r113. Epub 2009 Oct 14.


Background: Hypoxia-inducible factor 1 (HIF-1) plays a key role in cellular adaptation to hypoxia. To better understand the determinants of HIF-1 binding and transactivation, we used ChIP-chip and gene expression profiling to define the relationship between the epigenetic landscape, sites of HIF-1 binding, and genes transactivated by hypoxia in two cell lines.

Results: We found that when cells were acutely subjected to hypoxia, HIF-1 preferentially bound to loci that were already transcriptionally active under normal growth conditions characterized by the presence of histone H3 lysine 4 methylation, the presence of RNA polymerase II, and basal production of mRNA. Cell type-specific differences in HIF-1 binding were largely attributable to differences in the basal gene expression patterns in the cells prior to the onset of hypoxia.

Conclusions: These results suggest that the repertoire of genes active in a cell (for example, through lineage specific transcription factors) defines the subset of genes that are permissive for binding and transactivation by stimulus-responsive transcription factors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Hypoxia / genetics
  • Cell Line, Tumor
  • Gene Expression Regulation
  • Genetic Loci*
  • Humans
  • Hypoxia-Inducible Factor 1 / metabolism*
  • Models, Genetic
  • Organ Specificity / genetics*
  • Promoter Regions, Genetic
  • Protein Binding
  • Transcription, Genetic*


  • Hypoxia-Inducible Factor 1