Preferential binding of HIF-1 to transcriptionally active loci determines cell-type specific response to hypoxia.
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.
Xia
Xiaobo
X
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Children's Hospital Boston, and Harvard Medical School, Binney Street, Boston, MA 02115, USA. xiaobo_xia@dfci.harvard.edu
Kung
Andrew L
AL
D015687:Cell Hypoxia / Q000235:genetics; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation; D056426:Genetic Loci; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism*; D008957:Models, Genetic; D009928:Organ Specificity / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D014158:Transcription, Genetic
D051793:Hypoxia-Inducible Factor 1