Control of replication initiation and heterochromatin formation in Saccharomyces cerevisiae by a regulator of meiotic gene expression
Control of replication initiation and heterochromatin formation in Saccharomyces cerevisiae by a regulator of meiotic gene expression
复制标题
DOI：
10.1101/gad.334805
复制
发表时间：
2005-08-01
影响因子：
10.5
通讯作者：
Ehrenhofer-Murray, AE
中科院分区：
文献类型：
--
作者：
Irlbacher, H;Franke, J;Ehrenhofer-Murray, AE
酿酒酵母中沉默的交配型基因座HMR和HML的异染色质是通过一组与沉默分子结合的锚蛋白将SIR复合体靶向这些区域而实现的。在这里，我们已经确定了一种针对HML的新的异染色质靶向因子，即SUMI蛋白，它是营养生长过程中减数分裂基因的抑制因子。Sum1在体外和体内都通过HML-E消音器内的一个功能元件与HML结合，而Sum1 Delta引起HML去抑制。值得注意的是，Sum1也是HML-E起始活性所必需的，这证明了Sum1在复制启动中的作用。在对Sum1调控的起源的全基因组搜索中，我们鉴定了一组与起源识别复合体和Sum1结合的自主复制序列(ARS元件)。这些起始点的完全起始活性需要Sum1，并且它们的起始点活性在移除Sum1结合位点后降低。因此，Sum1在酵母中构成了一种新的复制起始的全球调控因子。
Heterochromatinization at the silent mating-type loci HMR and HML in Saccharomyces cerevisiae is achieved by targeting the Sir complex to these regions via a set of anchor proteins that bind to the silencers. Here, we have identified a novel heterochromatin-targeting factor for HML, the protein Sumi, a repressor of meiotic genes during vegetative growth. Sum1 bound both in vitro and in vivo to HML via a functional element within the HML-E silencer, and sum1 Delta caused HML derepression. Significantly, Sum1 was also required for origin activity of HML-E, demonstrating a role of Sum1 in replication initiation. In a genome-wide search for Sum1-regulated origins, we identified a set of autonomous replicative sequences (ARS elements) that bound both the origin recognition complex and Sum1. Full initiation activity of these origins required Sum1, and their origin activity was decreased upon removal of the Sum1-binding site. Thus, Sum1 constitutes a novel global regulator of replication initiation in yeast.