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

Abstract:

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.

journal_name

Genome Biol

journal_title

Genome biology

authors

Xia X,Kung AL

doi

10.1186/gb-2009-10-10-r113

subject

Has Abstract

pub_date

2009-01-01 00:00:00

pages

R113

issue

10

eissn

1474-7596

issn

1474-760X

pii

gb-2009-10-10-r113

journal_volume

10

pub_type

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