Targeted recruitment of Rpd3 histone deacetylase represses transcription by inhibiting recruitment of Swi/Snf, SAGA, and TATA binding protein.

Certain DNA-binding repressors inhibit transcription by recruiting Rpd3 histone deacetylase complexes to promoters and generating domains of histone deacetylation that extend over a limited number of nucleosomes. Here, we show that the degree of Rpd3-dependent repression depends on the activator and the level of activation, not the extent of histone deacetylation. In all cases tested, activator binding is unaffected by histone deacetylation. In contrast, Rpd3-dependent repression is associated with decreased occupancy by TATA binding protein (TBP), the Swi/Snf nucleosome-remodeling complex, and the SAGA histone acetylase complex. Transcriptional repression is bypassed by direct recruitment of TBP and several TBP-associated factors, but not by natural activation domains or direct recruitment of polymerase II holoenzyme components. These results suggest that the domain of localized histone deacetylation generated by recruitment of Rpd3 mediates repression by inhibiting recruitment of chromatin-modifying activities and TBP.