Histone deacetylase Rpd3 antagonizes Sir2-dependent silent chromatin propagation.
Histone deacetylase Rpd3 antagonizes Sir2-dependent silent chromatin propagation.
复制标题
组蛋白脱乙酰酶 Rpd3 拮抗 Sir2 依赖性沉默染色质增殖。
DOI：
10.1093/nar/gkp233
复制
发表时间：
2009-06
影响因子：
14.9
通讯作者：
Zhou JQ
中科院分区：
文献类型：
--
作者：
Zhou J;Zhou BO;Lenzmeier BA;Zhou JQ
在真核生物基因组中，转录沉默的染色质倾向于沿着染色体繁殖并侵入相邻的活性染色质。沉默机制可以被染色质边界元件所阻止。我们在酿酒酵母中进行了筛选，以寻找可能有助于建立染色质边界的蛋白质。我们发现，组蛋白去乙酰化酶Rpd3p的破坏导致有缺陷的边界活动，导致sir依赖的转录抑制的局部传播。在rpd3Δ细胞中，通常在核仁中发现的Sir2p的量减少，而在端粒和HM及其邻近位点发现的Sir2p的量增加，导致沉默染色质在这些区域的延伸。此外，Rpd3p直接与染色质在边界区域相互作用，使组蛋白H4在赖氨酸5和赖氨酸12处脱乙酰化。无论是组蛋白H4在赖氨酸5或组蛋白乙酰转移酶（HAT）的Esa1p活性的降低突变废除了沉默表型与Rpd3突变，这表明一个新的作用Rpd3p介导的异染色质边界调节的H4氨基末端。总之，这些数据提供了深入了解在异染色质边界形成过程中Rpd3p的抗沉默功能的分子机制。
In the eukaryotic genome, transcriptionally silent chromatin tends to propagate along a chromosome and encroach upon adjacent active chromatin. The silencing machinery can be stopped by chromatin boundary elements. We performed a screen in Saccharomyces cerevisiae for proteins that may contribute to the establishment of a chromatin boundary. We found that disruption of histone deacetylase Rpd3p results in defective boundary activity, leading to a Sir-dependent local propagation of transcriptional repression. In rpd3Δ cells, the amount of Sir2p that was normally found in the nucleolus decreased and the amount of Sir2p found at telomeres and at HM and its adjacent loci increased, leading to an extension of silent chromatin in those areas. In addition, Rpd3p interacted directly with chromatin at boundary regions to deacetylate histone H4 at lysine 5 and at lysine 12. Either the mutation of histone H4 at lysine 5 or a decrease in the histone acetyltransferase (HAT) activity of Esa1p abrogated the silencing phenotype associated with rpd3 mutation, suggesting a novel role for the H4 amino terminus in Rpd3p-mediated heterochromatin boundary regulation. Together, these data provide insight into the molecular mechanisms for the anti-silencing functions of Rpd3p during the formation of heterochromatin boundaries.
登录
查看更多内容
影响因子：
5.3
作者：
Braglia, Priscilla;Dugas, Sandra L.;Dieci, Giorgio
通讯作者：
Dieci, Giorgio
影响因子：
10.5
作者：
Donze, D;Adams, CR;Kamakaka, RT
通讯作者：
Kamakaka, RT
影响因子：
4.8
作者：
Carmen, AA;Milne, L;Grunstein, M
通讯作者：
Grunstein, M
影响因子：
16
作者：
Govind, Chhabi K.;Zhang, Fan;Hinnebusch, Alan G.
通讯作者：
Hinnebusch, Alan G.
影响因子：
10.5
作者：
Bi, X;Broach, JR
通讯作者：
Broach, JR