Isw1 Functions in Parallel with the NuA4 and Swr1 Complexes in Stress-Induced Gene Repression

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.