Interplay of TBP Inhibitors in Global Transcriptional Control

The TATA binding protein (TBP)is required for the utes to the steric occlusion of TFIIB. A yeast TBP mutaexpression of nearly all genes and is highly regulated tion (F182V)along this interface disrupts TBP/NC2 interboth positively and negatively. Here, we use DNA mi- actions in vitro and causes increased expression of a croarrays to explore the genome-wide interplay of sev- number of enhancerless genes in vivo (Cang et al., 1999). eral TBP-interacting inhibitors in the yeast Saccharo- NC2 overexpression selectively suppresses phenotypes myces cerevisiae. Our findings suggest the following: associated with this mutation, providing further evi- The NC2 inhibitor turns down, but not off, highly active dence that TBP (F182V)is primarily defective in NC2 genes. Autoinhibition of TBP through dimerization interactions. In addition to acting as an inhibitor, NC2 contributes to transcriptional repression, even at re- plays a positive role in transcription, although its basis pressive subtelomeric regions. The TAND domain of is not understood (Cang et al., 1999; Geisberg et al., TAF1 plays a primary inhibitory role at very few genes, 2001; Willy et al., 2000). but its function becomes widespread when other TBP TAF1 inhibits TBP/TATA interactions (Banik et al., interactions are compromised. These findings reveal 2001; Kokubo et al., 1998; Nishikawa et al., 1997). NMR that transcriptional output is limited in part by a collab- analysis of the Drosophila TAF1 amino-terminal domain oration of different combinations of TBP inhibitory I (TAND I)indicates that it engages in molecular mimicry mechanisms.