title: Facilitated binding of TATA-binding protein to nucleosomal DNA.
abstract: BINDING of the TATA-binding protein (TBP) to the TATA box is required for transcription from many eukaryotic promoters in gene expression. Regulation of this binding is therefore likely to be an important determinant of promoter activity. Incorporation of the TATA sequence into nucleosomes dramatically reduces transcription initiation, presumably because of stereochemical constraints on binding of general transcription factors. Biochemical and genetic studies imply that cellular factors such as yeast SWI/SNF are required for activator function and might alter chromatin structure. One step that could be regulated during the activation process is TBP binding in chromatin 12, 13. We show here that binding of TBP to the TATA sequence is severely inhibited 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 to the surface of the histone core affects the access of TBP. We propose that the dynamic remodelling of chromatin structure to allow TBP binding is a key step in the regulation of eukaryotic gene expression.
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Boston 02114.
authors.forename: A N
authors.initials: AN
authors.lastname: Imbalzano
authors.forename: H
authors.initials: H
authors.lastname: Kwon
authors.forename: M R
authors.initials: MR
authors.lastname: Green
authors.forename: R E
authors.initials: RE
authors.lastname: Kingston
mesh_terms: D000251:Adenosine Triphosphatases; D004247:DNA / Q000378:metabolism*; D004265:DNA Helicases; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins; D009707:Nucleosomes / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D011994:Recombinant Proteins; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D016385:TATA Box; D035181:TATA-Box Binding Protein; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D009707:Nucleosomes; D011994:Recombinant Proteins; C499336:SMARCA1 protein, human; C084011:SMARCA2 protein, human; D029701:Saccharomyces cerevisiae Proteins; D035181:TATA-Box Binding Protein; D014157:Transcription Factors; D004247:DNA; D000251:Adenosine Triphosphatases; C084108:SMARCA4 protein, human; C499333:SNF2 protein, S cerevisiae; D004265:DNA Helicases