Widespread collaboration of Isw2 and Sin3-Rpd3 chromatin remodeling complexes in transcriptional repression

The yeast Isw2 chromatin remodeling complex functions in parallel with the Sin3-Rpd3 histone deacetylase complex to repress early meiotic genes upon r ecruitment by Ume6p. For many of these genes, the effect of an isw2 mutatio n is partially masked by a functional Sin3-Rpd3 complex. To identify the fu ll range of genes repressed or activated by these factors and uncover hidde n targets of Isw2-dependent regulation, we performed full genome expression analyses using cDNA microarrays. We find that the Isw2 complex functions m ainly in repression of transcription in a parallel pathway with the Sin3-Rp d3 complex. In addition to Ume6 target genes, we find that many Ume6-indepe ndent genes are derepressed in mutants lacking functional Isw2 and Sin3-Rpd 3 complexes. Conversely, we find that ume6 mutants, but not isw2 sin3 or is w2 rpd3 double mutants, have reduced fidelity of mitotic chromosome segrega tion, suggesting that one or more functions of Ume6p are independent of Sin 3-Rpd3 and Isw2 complexes. Chromatin structure analyses of two nonmeiotic g enes reveals increased DNase I sensitivity within their regulatory regions in an isw2 mutant, as seen previously for one meiotic locus. These data sug gest that the Isw2 complex functions at Ume6-dependent and -independent loc i to create DNase I-inaccessible chromatin structure by regulating the posi tioning or placement of nucleosomes.