Hypoxic response is driven by the BAF form of SWI/SNF
Tran, K. D.; Chakravarty, T.; Garzon, J.; Saraf, A.; Florens, L.; Washburn, M.; Dutta, A.
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SWI/SNF has been shown to have important functions in hypoxia-mediated gene expression through roles of its catalytic and core subunits. Since SWI/SNF exists as three distinct assemblies, and usage of complex specific subunits of the complex can be expected to vary within a given cell under changing environmental conditions. It remains an open question as to the compositional makeup of SWI/SNF and the roles of individual complexes in gene expression and cell viability in a hypoxic environment. In our current study, we find that hypoxia regulates levels of unique subunits that define each complex. Protein levels of ARID2 and PBRM1, members of PBAF and BRD9, a member of ncBAF, are downregulated in hypoxic cells, while members of BAF complex are retained. Our studies further show that loss of ARID1A, ARID1B and DPF2, which are unique subunits of BAF, reduces induction of HIF target genes and ARID1A or DPF2 are important for cell survival during hypoxia. Collectively, our results provide evidence that levels of SWI/SNF forms are not static within cells, but can be dynamically altered as a response to environmental changes.
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