The Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Southeast University, Nanjing 210096, China.
Biochem Biophys Res Commun. 2013 Sep 6;438(4):746-52. doi: 10.1016/j.bbrc.2013.07.096. Epub 2013 Jul 31.
In Saccharomyces cerevisiae, subtelomeric silencing is involved in the propagation of Silent Information Regulator (SIR) proteins toward euchromatin. Numerous mechanisms are involved in antagonizing the local spread of Sir-dependent silent chromatin into neighboring euchromatin. Here, we identified a novel role for sumoylation E3 ligase Mms21 in the maintenance of subtelomeric silencing. We found that disruption of E3 ligase activity of Mms21 results in the de-repression of subtelomeric silencing. Deletion of E3 ligase domain of Mms21 led to decreased binding of Sir2p, Sir3p and Sir4 at subtelomeric chromatins and increased H3K4 tri-methylation at telomere-distal euchromatin regions, correlating with increased gene expression in two subtelomeric reporter genes. In addition, a mms21Δsl mutant caused a severe growth defect in combination with htz1Δ deletion and showed an enhanced association of Htz1 with telomere proximal regions. Taken together, our findings suggest an important role of Mms21p; it contributes to subtelomeric silencing during the formation of a heterochromatin boundary.
在酿酒酵母中，端粒沉默参与了沉默信息调节因子（SIR）蛋白向常染色质的传播。有许多机制参与拮抗 Sir 依赖性沉默染色质在邻近常染色质中的局部扩散。在这里，我们发现了 SUMO 连接酶 Mms21 在维持端粒沉默中的一个新作用。我们发现，破坏 Mms21 的 E3 连接酶活性会导致端粒沉默的去抑制。Mms21 的 E3 连接酶结构域缺失导致 Sir2p、Sir3p 和 Sir4 在端粒染色质上的结合减少，以及端粒远端常染色质区域 H3K4 三甲基化增加，与两个端粒报告基因的表达增加相关。此外，mms21Δsl 突变体与 htz1Δ 缺失结合时会导致严重的生长缺陷，并显示出 Htz1 与端粒近端区域的增强关联。总之，我们的研究结果表明，Mms21p 发挥着重要作用；它有助于异染色质边界形成过程中的端粒沉默。
