1. Integrative analysis of HIF binding and transactivation reveals its role in maintaining histone methylation homeostasis
- Author
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Xia, Xiaobo, Lemieux, Madeleine E., Li, Wei, Carroll, Jason S., Brown, Myles, Liu, X. Shirley, and Kung, Andrew L.
- Subjects
Histones -- Properties ,Hypoxia -- Physiological aspects ,Homeostasis -- Evaluation ,Science and technology - 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. ChIP-chip | hypoxia | jumonji protein | dioxygenase | epigenetics
- Published
- 2009