Hirschhorn J N, Brown S A, Clark C D, Winston F
Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115.
Genes Dev. 1992 Dec;6(12A):2288-98. doi: 10.1101/gad.6.12a.2288.
Changes in chromatin structure have frequently been correlated with changes in transcription. However, the cause-and-effect relationship between chromatin structure and transcription has been hard to determine. In addition, identifying the proteins that regulate chromatin structure has been difficult. Recent evidence suggests that a functionally related set of yeast transcriptional activators (SNF2/SWI2, SNF5, SNF6, SWI1, and SWI3), required for transcription of a diverse set of genes, may affect chromatin structure. We now present genetic and molecular evidence that at least two of these transcriptional activators, SNF2/SWI2 and SNF5, function by antagonizing repression mediated by nucleosomes. First, the transcriptional defects in strains lacking these SNF genes are suppressed by a deletion of one of the two sets of genes encoding histones H2A and H2B, (hta1-htb1) delta. Second, at one affected promoter (SUC2), chromatin structure is altered in snf2/swi2 and snf5 mutants, and this chromatin defect is suppressed by (hta1-htb1) delta. Finally, analysis of chromatin structure at a mutant SUC2 promoter, in which the TATA box has been destroyed, demonstrates that the differences in SUC2 chromatin structure between SNF5+ and snf5 mutant strains are not simply an effect of different levels of SUC2 transcription. Thus, these results strongly suggest that SNF2/SWI2 and SNF5 cause changes in chromatin structure and that these changes allow transcriptional activation.
染色质结构的变化常常与转录的变化相关。然而，染色质结构与转录之间的因果关系一直难以确定。此外，鉴定调控染色质结构的蛋白质也很困难。最近的证据表明，一组功能相关的酵母转录激活因子（SNF2/SWI2、SNF5、SNF6、SWI1和SWI3），是多种基因转录所必需的，可能会影响染色质结构。我们现在提供遗传和分子证据，表明这些转录激活因子中至少有两个，即SNF2/SWI2和SNF5，通过拮抗核小体介导的抑制作用来发挥功能。首先，缺乏这些SNF基因的菌株中的转录缺陷，可被编码组蛋白H2A和H2B的两组基因之一（hta1-htb1）δ的缺失所抑制。其次，在一个受影响的启动子（SUC2）处，snf2/swi2和snf5突变体中的染色质结构发生了改变，而这种染色质缺陷被（hta1-htb1）δ所抑制。最后，对一个突变的SUC2启动子的染色质结构分析表明，其中TATA框已被破坏，SNF5+和snf5突变体菌株之间SUC2染色质结构的差异并非仅仅是不同水平的SUC2转录的结果。因此，这些结果强烈表明，SNF2/SWI2和SNF5会导致染色质结构的变化，并且这些变化允许转录激活。
