Genome-wide location analysis indicates that the yeast nucleosome-remodeling complex RSC has approximately 700 physiological targets and that the Rsc1 and Rsc2 isoforms of the complex behave indistinguishably. RSC is associated with numerous tRNA promoters, suggesting that the complex is recruited by the RNA polymerase III transcription machinery. At RNA polymerase II promoters, RSC specifically targets several gene classes, including histones, small nucleolar RNAs, the nitrogen discrimination pathway, nonfermentative carbohydrate metabolism, and mitochondrial function. At the histone HTA1/HTB1 promoter, RSC recruitment requires the Hir1 and Hir2 corepressors, and it is associated with transcriptional inactivity. In contrast, RSC binds to promoters involved in carbohydrate metabolism in response to transcriptional activation, but prior to association of the Pol II machinery. Therefore, the RSC complex is generally recruited to Pol III promoters and it is specifically recruited to Pol II promoters by transcriptional activators and repressors.