A role for TBP dimerization in preventing unregulated gene expression

The recruitment of the TATA box-binding protein (TBP) to promoters in vivo is often rate limiting in gene expression. We present evidence that TBP neg atively autoregulates its accessibility to promoter DNA in yeast through di merization. The crystal structure of TBP dimers was used to design point mu tations in the dimer interface. These mutants are impaired for dimerization in vitro, and in vivo they generate large increases in activator-independe nt gene expression. Overexpression of wild-type TBP suppresses these mutant s, possibly by heterodimerizing with them. In addition to loss of autorepre ssion, dimerization-defective TBPs are rapidly degraded in vivo. Direct det ection of TBP dimers in vivo was achieved through chemical cross-linking. T aken together, the data suggest that TBP dimerization prevents unregulated gene expression and its own degradation.