Kwon H, Imbalzano A N, Khavari P A, Kingston R E, Green M R
Howard Hughes Medical Institute, Program in Molecular Medicine, University of Massachusetts Medical Center, Worcester 01605.
Nature. 1994 Aug 11;370(6489):477-81. doi: 10.1038/370477a0.
CHROMATIN structure can affect the transcriptional activity of eukaryotic structural genes by blocking access of sequence-specific activator proteins (activators) to their promoter-binding sites. For example, the DNA-binding domain of the yeast GAL4 protein interacts very poorly with nucleosome cores compared with naked DNA2 (and see below), and binding of other activators is even more strongly inhibited. The way in which activators bind to nucleosomal DNA is therefore a critical aspect of transcriptional activation. Genetic studies have suggested that the multi-component SWI/SNF complex of Saccharomyces cerevisiae facilitates transcription by altering the structure of the chromatin. Here we identify and partially purify a human homologue of the yeast SWI/SNF complex (hSWI/SNF complex). We show that a partially purified hSWI/SNF complex mediates the ATP-dependent disruption of a nucleosome, thereby enabling the activators, GAL4-VP16 and GAL4-AH, to bind within a nucleosome core. We conclude that the hSWI/SNF complex acts directly to reorganize chromatin structure so as to facilitate binding of transcription factors.
染色质结构可通过阻止序列特异性激活蛋白（激活因子）与其启动子结合位点的结合，来影响真核生物结构基因的转录活性。例如，与裸露DNA相比，酵母GAL4蛋白的DNA结合结构域与核小体核心的相互作用非常弱（见下文），而其他激活因子的结合受到的抑制更强。因此，激活因子与核小体DNA的结合方式是转录激活的关键环节。遗传学研究表明，酿酒酵母的多组分SWI/SNF复合物通过改变染色质结构促进转录。在此，我们鉴定并部分纯化了酵母SWI/SNF复合物的人源同源物（hSWI/SNF复合物）。我们发现，部分纯化的hSWI/SNF复合物介导了核小体的ATP依赖性破坏，从而使激活因子GAL4-VP16和GAL4-AH能够在核小体核心内结合。我们得出结论，hSWI/SNF复合物直接作用于重组染色质结构，以促进转录因子的结合。
