FACILITATED BINDING OF TATA-BINDING PROTEIN TO NUCLEOSOMAL DNA

BINDING of the TATA-binding protein (TBP) to the TATA box is required for transcription from many eukaryotic promoters in gene expression. R egulation of this binding is therefore likely to be an important deter minant of promoter activity. Incorporation of the TATA sequence into n ucleosomes dramatically reduces transcription initiation(1-3), presuma bly because of stereochemical constraints on binding of general transc ription factors. Biochemical and genetic studies imply that cellular f actors such as yeast SWI/SNF are required for activator function and m ight alter chromatin structure(4-11). One step that could be regulated during the activation process is TBP binding in chromatin(12,13) We s how here that binding of TBP to the TATA sequence is severely inhibite d by incorporation of this sequence into a nucleosome. Inhibition can be overcome by ATP-dependent alterations in nucleosomal DNA structure mediated by hSWI/SNF, a putative human homologue of the yeast SWI/SNF complex. Additionally, the orientation of the TATA sequence relative t o the surface of the histone core affects the access of TBP. We propos e that the dynamic remodelling of chromatin structure to allow TBP bin ding is a key step in the regulation of eukaryotic gene expression.