Veis J, Klug H, Koranda M, Ammerer G
Max F. Perutz Laboratories, University Departments at the Vienna Biocenter, Department of Biochemistry, University of Vienna, Dr. Bohrgasse 9, 1030 Vienna, Austria.
Mol Cell Biol. 2007 Dec;27(23):8364-73. doi: 10.1128/MCB.01253-07. Epub 2007 Oct 1.
In budding yeast (Saccharomyces cerevisiae), the periodic expression of the G2/M-specific gene CLB2 depends on a DNA binding complex that mediates its repression during G1 and activation from the S phase to the exit of mitosis. The switch from low to high expression levels depends on the transcriptional activator Ndd1. We show that the inactivation of the Sin3 histone deacetylase complex bypasses the essential role of Ndd1 in cell cycle progression. Sin3 and its catalytic subunit Rpd3 associate with the CLB2 promoter during the G1 phase of the cell cycle. Both proteins dissociate from the promoter at the onset of the S phase and reassociate during G2 phase. Sin3 removal coincides with a transient increase in histone H4 acetylation followed by the expulsion of at least one nucleosome from the promoter region. Whereas the first step depends on Cdc28/Cln1 activity, Ndd1 function is required for the second step. Since the removal of Sin3 is independent of Ndd1 recruitment and Cdc28/Clb activity it represents a unique regulatory step which is distinct from transcriptional activation.
在出芽酵母(酿酒酵母)中,G2/M特异性基因CLB2的周期性表达依赖于一种DNA结合复合物,该复合物在G1期介导其抑制作用,并在从S期到有丝分裂退出期间介导其激活作用。从低表达水平到高表达水平的转变取决于转录激活因子Ndd1。我们发现,Sin3组蛋白去乙酰化酶复合物的失活绕过了Ndd1在细胞周期进程中的关键作用。Sin3及其催化亚基Rpd3在细胞周期的G1期与CLB2启动子结合。这两种蛋白质在S期开始时从启动子上解离,并在G2期重新结合。Sin3的去除与组蛋白H4乙酰化的短暂增加同时发生,随后至少一个核小体从启动子区域被驱逐。虽然第一步依赖于Cdc28/Cln1活性,但第二步需要Ndd1发挥作用。由于Sin3的去除独立于Ndd1的募集和Cdc28/Clb活性,它代表了一个独特的调控步骤,与转录激活不同。