Abstract
Hypoxia induces a variety of cellular responses such as cell cycle arrest, apoptosis, and autophagy. Most of these responses are mediated by the hypoxia-inducible factor-1 alpha. To induce target genes, hypoxia-inducible factor-1 alpha requires a chromatin environment conducive to allow binding to specific sequences. Here, we have studied the role of the chromatin-remodeling complex SWI/SNF in the cellular response to hypoxia. We find that SWI/SNF is required for several of the cellular responses induced by hypoxia. Surprisingly, hypoxia-inducible factor-1 alpha is a direct target of the SWI/SNF chromatin-remodeling complex. SWI/SNF components are found associated with the hypoxia-inducible factor-1 alpha promoter and modulation of SWI/SNF levels results in pronounced changes in hypoxia-inducible factor-1 alpha expression and its ability to transactivate target genes. Furthermore, impairment of SWI/SNF function renders cells resistant to hypoxia-induced cell cycle arrest. These results reveal a previously uncharacterized dependence of hypoxia signaling on the SWI/SNF complex and demonstrate a new level of control over the hypoxia-inducible factor-1 alpha system.
| Original language | English |
|---|---|
| Pages (from-to) | 4123-4131 |
| Number of pages | 9 |
| Journal | Journal of Biological Chemistry |
| Volume | 284 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 13 Feb 2009 |
Keywords
- NF-KAPPA-B
- CHROMATIN-REMODELING COMPLEX
- ARF TUMOR-SUPPRESSOR
- GENE-EXPRESSION
- INDUCIBLE FACTOR-1-ALPHA
- PROTEASOMAL DEGRADATION
- VASCULAR DEVELOPMENT
- HIF-1-ALPHA
- SUBUNIT
- IDENTIFICATION