Triolo T, Sternglanz R
Department of Biochemistry and Cell Biology, State University of New York, Stony Brook, 11794, USA.
Nature. 1996 May 16;381(6579):251-3. doi: 10.1038/381251a0.
Transcriptional silencing of the HM mating-type loci in the yeast Saccharomyces cerevisiae is caused by the localized formation of an altered chromatin structure, analogous to heterochromatin in higher eukaryotes. Silencing depends on cis-acting sequences, termed silencers, as well as several trans-acting factors, including histones H4 and H3, proteins RAP1 and ABF1, and the four SIR proteins (SIR1-4). Each of the four HM silencers contains an autonomously replicating sequence (ARS) to which the origin replication complex (ORC) binds. This six-protein complex is required for initiation of DNA replication, as well as for silencing. Efficient establishment of the silenced state requires both passage through the S phase of the cell cycle and SIR1 protein. Previous experiments suggested that SIR1 might be localized to the silencers by binding to ORC and/or RAP1. Here we report that SIR1 can bind directly to ORC1, the largest of the ORC subunits, and that targeting of SIR1 to ORC1 at a silencer is sufficient to establish a silenced state.
酿酒酵母中HM交配型基因座的转录沉默是由一种改变的染色质结构的局部形成引起的，类似于高等真核生物中的异染色质。沉默依赖于顺式作用序列（称为沉默子）以及几种反式作用因子，包括组蛋白H4和H3、RAP1和ABF1蛋白，以及四种SIR蛋白（SIR1 - 4）。四个HM沉默子中的每一个都包含一个自主复制序列（ARS），起始复制复合物（ORC）与之结合。这个六蛋白复合物对于DNA复制的起始以及沉默都是必需的。沉默状态的有效建立需要通过细胞周期的S期以及SIR1蛋白。先前的实验表明，SIR1可能通过与ORC和/或RAP1结合而定位到沉默子上。在这里我们报告，SIR1可以直接与ORC1（ORC最大的亚基）结合，并且在沉默子处将SIR1靶向ORC1足以建立沉默状态。
