Imbalzano A N, Kwon H, Green M R, Kingston R E
Department of Molecular Biology, Massachusetts General Hospital, Boston 02114.
Nature. 1994 Aug 11;370(6489):481-5. doi: 10.1038/370481a0.
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.
在基因表达过程中，许多真核生物启动子的转录需要TATA结合蛋白（TBP）与TATA盒结合。因此，这种结合的调控可能是启动子活性的一个重要决定因素。将TATA序列整合到核小体中会显著降低转录起始，推测这是由于对一般转录因子结合的立体化学限制。生化和遗传学研究表明，酵母SWI/SNF等细胞因子是激活功能所必需的，并且可能改变染色质结构。激活过程中一个可能受到调控的步骤是TBP在染色质中的结合12,13。我们在此表明，如果将该序列整合到核小体中，TBP与TATA序列的结合会受到严重抑制。这种抑制可以通过由hSWI/SNF介导的核小体DNA结构的ATP依赖性改变来克服，hSWI/SNF是酵母SWI/SNF复合物的一种假定人类同源物。此外，TATA序列相对于组蛋白核心表面的方向会影响TBP的接近程度。我们提出，染色质结构的动态重塑以允许TBP结合是真核基因表达调控中的关键步骤。
