SWI/SNF regulates the cellular response to hypoxia

Niall S. Kenneth, Sharon Mudie, Patrick van Uden, Sonia Rocha

    Research output: Contribution to journalArticlepeer-review

    84 Citations (Scopus)

    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 languageEnglish
    Pages (from-to)4123-4131
    Number of pages9
    JournalJournal of Biological Chemistry
    Volume284
    Issue number7
    DOIs
    Publication statusPublished - 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

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