Jiang Y W, Dohrmann P R, Stillman D J
Department of Cellular, Viral, and Molecular Biology, University of Utah Medical Center, Salt Lake City 84132, USA.
Genetics. 1995 May;140(1):47-54. doi: 10.1093/genetics/140.1.47.
The SIN4 and RGR1 genes of Saccharomyces cerevisiae were identified by mutations in quite different genetic screens. We have shown that the SIN4 gene product is required for proper transcriptional regulation of many genes and that a sin4 mutation can affect either activation or repression of specific genes. We have suggested that this dual nature of SIN4 in transcriptional regulation is due to its involvement in chromatin organization. We now report that the role of RGR1 in gene regulation is similar to that of SIN4. SIN4 and RGR1 both function as negative transcriptional regulators of HO and IME1, and mutations in either gene lead to decreased expression of other genes including CTS1. Strains with sin4 or rgr1 mutations both have phenotypes similar to those caused by histone mutations, including suppression of delta insertion into promoters (Spt- phenotype), activation of promoters lacking UAS elements, and decreased superhelical density of plasmid DNA molecules. Overexpression of RGR1 suppresses the temperature sensitivity due to a sin4 mutation. Finally, we use yeast strains expressing GST fusion proteins to demonstrate that the Sin4p and Rgr1p proteins are physically associated in vivo. These results indicate that Sin4p and Rgr1p act together in vivo to organize chromatin structure and thus regulate transcription.
酿酒酵母的SIN4和RGR1基因是通过在截然不同的遗传筛选中发生的突变而鉴定出来的。我们已经表明，SIN4基因产物是许多基因正确转录调控所必需的，并且sin4突变可以影响特定基因的激活或抑制。我们认为，SIN4在转录调控中的这种双重性质是由于其参与染色质组织。我们现在报告，RGR1在基因调控中的作用与SIN4相似。SIN4和RGR1均作为HO和IME1的负转录调节因子发挥作用，任一基因的突变都会导致包括CTS1在内的其他基因表达降低。具有sin4或rgr1突变的菌株都具有与组蛋白突变引起的表型相似的表型，包括抑制δ插入启动子（Spt-表型）、激活缺乏UAS元件的启动子以及降低质粒DNA分子的超螺旋密度。RGR1的过表达抑制了由于sin4突变引起的温度敏感性。最后，我们使用表达GST融合蛋白的酵母菌株来证明Sin4p和Rgr1p蛋白在体内存在物理关联。这些结果表明，Sin4p和Rgr1p在体内共同作用以组织染色质结构，从而调节转录。
