Noncompetitive counteractions of DNA polymerase ε and ISW2/yCHRAC for epigenetic inheritance of telomere position effect in Saccharomyces cerevisiae
Noncompetitive counteractions of DNA polymerase ε and ISW2/yCHRAC for epigenetic inheritance of telomere position effect in Saccharomyces cerevisiae
复制标题
DOI：
10.1128/mcb.24.1.217-227.2004
复制
发表时间：
2004-01-01
影响因子：
5.3
通讯作者：
Araki, H
中科院分区：
文献类型：
--
作者：
Iida, T;Araki, H
常染色质基因在异染色质区域附近的重新定位常常导致嵌合基因沉默。在酿酒酵母中，在端粒异染色质样区域插入基因的细胞显示出被称为端粒位置效应的表型杂色，并且表观遗传状态稳定地传递给后代。在这里，我们表明，端粒基因的表观遗传状态是不稳定的细胞中，无论是携带复制型DNA聚合酶（Poll）的催化亚基（Pol 2）的突变或缺乏一个非必需的和组蛋白折叠基序的Poll，DPB 3和DPB 4的亚基。我们还报告了一种新的和推定的染色质重塑复合物，ISW 2/yCHRAC，它包含Isw 2，Itc 1，Dpb 3样亚基（Dls 1）和Dpb 4。使用本研究中开发的单细胞方法，我们证明了在没有Pol和ISW 2/yCHRAC的情况下，端粒的表观遗传状态频繁切换。此外，我们发现，Pol和ISW 2/yCHRAC功能独立：Pol的沉默状态的稳定继承，而ISW 2/yCHRAC的表达状态的工作。因此，我们提出，端粒的特定表观遗传状态的遗传需要至少两个抵消监管机构。
Relocation of euchromatic genes near the heterochromatin region often results in mosaic gene silencing. In Saccharomyces cerevisiae, cells with the genes inserted at telomeric heterochromatin-like regions show a phenotypic variegation known as the telomere-position effect, and the epigenetic states are stably passed on to following generations. Here we show that the epigenetic states of the telomere gene are not stably inherited in cells either bearing a mutation in a catalytic subunit (Pol2) of replicative DNA polymerase epsilon (Pol epsilon) or lacking one of the nonessential and histone fold motif-containing subunits of Pol epsilon, Dpb3 and Dpb4. We also report a novel and putative chromatin-remodeling complex, ISW2/yCHRAC, that contains Isw2, Itc1, Dpb3-like subunit (Dls1), and Dpb4. Using the single-cell method developed in this study, we demonstrate that without Pol epsilon and ISW2/yCHRAC, the epigenetic states of the telomere are frequently switched. Furthermore, we reveal that Pol epsilon and ISW2/yCHRAC function independently: Pol epsilon operates for the stable inheritance of a silent state, while ISW2/yCHRAC works for that of an expressed state. We therefore propose that inheritance of specific epigenetic states of a telomere requires at least two counteracting regulators.