Mammalian SWI-SNF complexes contribute to activation of the hsp70 gene

ATP-dependent chromatin-remodeling complexes are conserved among all eukary otes and function by altering nucleosome structure to allow cellular regula tory factors access to the DNA. Mammalian SWI-SNF complexes contain either of two highly conserved ATPase subunits: BRG1 or BRM. To identify cellular genes that require mammalian SWI-SNF complexes for the activation of gene e xpression, we have generated cell lines that inducibly express mutant forms of the BRG1 or BRM ATPases that are unable to bind and hydrolyze ATP. The mutant subunits physically associate with at least two endogenous members o f mammalian SWI-SNF complexes, suggesting that nonfunctional, dominant nega tive complexes may be formed. We determined that expression of the mutant B RG1 or BRM proteins impaired the ability of cells to activate the endogenou s stress response gene hsp70 in response to arsenite, a metabolic inhibitor , or cadmium, a heavy metal. Activation of hsp70 by heat stress, however, w as unaffected. Activation of the heme oxygenase 1 promoter by arsenite or c admium and activation of the cadmium-inducible metallothionein promoter als o were unaffected by the expression of mutant SWI-SNF components. Analysis of a subset of constitutively expressed genes revealed no or minimal effect s on transcript levels. We propose that the requirement for mammalian SWI-S NF complexes in gene activation events will be specific to individual genes and signaling pathways.