Integrative analysis of HIF binding and transactivation reveals its role in maintaining histone methylation homeostasis.
- Abstract:
- Adaptation to hypoxia is mediated through a coordinated transcriptional response driven largely by hypoxia-inducible factor 1 (HIF-1). We used ChIP-chip and gene expression profiling to identify direct targets of HIF-1 transactivation on a genome-wide scale. Several hundred direct HIF-1 targets were identified and, as expected, were highly enriched for proteins that facilitate metabolic adaptation to hypoxia. Surprisingly, there was also striking enrichment for the family of 2-oxoglutarate dioxygenases, including the jumonji-domain histone demethylases. We demonstrate that these histone demethylases are direct HIF targets, and their up-regulation helps maintain epigenetic homeostasis under hypoxic conditions. These results suggest that the coordinated increase in expression of several oxygen-dependent enzymes by HIF may help compensate for decreased levels of oxygen under conditions of cellular hypoxia.
- Authors:
- X Xia, ME Lemieux, W Li, JS Carroll, M Brown, XS Liu, AL Kung
- Journal:
- Proc Natl Acad Sci U S A
- Citation info:
- 106(11):4260-4265
- Publication date:
- 17th Mar 2009
- Full text
- DOI