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The packaging of DNA into chromatin allows eukaryotic cells to organize and compact their genomes but also creates an environment that is generally repressive to nuclear processes that depend upon DNA accessibility. There are several classes of enzymes that modulate the primary structure of chromatin to regulate various DNA-dependent processes. The biochemical activities of the yeast Isw1 ATP-dependent chromatin-remodeling enzyme have been well characterized in vitro, but little is known about how these activities are utilized in vivo. In this work, we sought to discern genetic backgrounds that require Isw1 activity for normal growth. We identified a three-way genetic interaction among Isw1, the NuA4 histone acetyltransferase complex, and the Swr1 histone replacement complex. Transcription microarray analysis revealed parallel functions for these three chromatin-modifying factors in the regulation of TATA-containing genes, including the repression of a large number of stress-induced genes under normal growth conditions. In contrast to a recruitment-based model, we find that the NuA4 and Swr1 complexes act throughout the genome while only a specific subset of the genome shows alterations in transcription.

There are several classes of ATP-dependent chromatin remodeling complexes, which modulate the structure of chromatin to regulate a variety of cellular processes. The budding yeast, Saccharomyces cerevisiae, encodes two ATPases of the ISWI class, Isw1p and Isw2p. Previously Isw1p was shown to copurify with three other proteins. Here we identify these associated proteins and show that Isw1p forms two separable complexes in vivo (designated Isw1a and Isw1b). Biochemical assays revealed that while both have equivalent nucleosome-stimulated ATPase activities, Isw1a and Isw1b differ in their abilities to bind to DNA and nucleosomal substrates, which possibly accounts for differences in specific activities in nucleosomal spacing and sliding. In vivo, the two Isw1 complexes have overlapping functions in transcriptional regulation of some genes yet distinct functions at others. In addition, these complexes show different contributions to cell growth at elevated temperatures.