Pericentric H3K9me3 Formation by HP1 Interaction-defective Histone Methyltransferase Suv39h1.
Pericentric H3K9me3 Formation by HP1 Interaction-defective Histone Methyltransferase Suv39h1.
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DOI：
10.1247/csf.16013
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发表时间：
2016-10
影响因子：
1.5
通讯作者：
Daisuke Muramatsu;H. Kimura;Kaoru Kotoshiba;M. Tachibana;Y. Shinkai
中科院分区：
文献类型：
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作者：
Daisuke Muramatsu;H. Kimura;Kaoru Kotoshiba;M. Tachibana;Y. Shinkai
着丝粒周围区域形成表观遗传学上有组织的沉默异染色质结构，其积累组蛋白H3赖氨酸9三甲基化（H3 K9 me 3）和异染色质蛋白1（HP 1），一种甲基化的H3 K9结合蛋白。在臂间区，Suv 39 h是产生H3 K9 me 3的主要酶。Suv 39 h也直接与HP 1相互作用。然而，HP 1相互作用对Suv 39 h介导的H3 K9 me 3在近着丝粒形成的重要性还没有得到很好的表征。为了解决这个问题，我们将HP 1结合缺陷的N端截短的小鼠Suv 39 h1（ΔN）引入Suv 39 h缺陷细胞中。内源性ΔN表达未检测到着丝粒周H3 K9 me 3阳性细胞。值得注意的是，如果Δ N过表达，则ΔN可以诱导H3 K9 me 3的臂间积累，如野生型Suv 39 h1所做的那样。这些发现表明，Suv 39 h1的N-末端区域，推测通过HP 1-Suv 39 h1相互作用，是Suv 39 h1介导的臂间H3 K9 me 3形成所需的，但如果Suv 39 h1过量产生，则可以被覆盖，表明Suv 39 h1介导的异染色质形成由多个模块控制，包括HP 1。
Pericentric regions form epigenetically organized, silent heterochromatin structures that accumulate histone H3 lysine 9 tri-methylation (H3K9me3) and heterochromatin protein 1 (HP1), a methylated H3K9-binding protein. At pericentric regions, Suv39h is the major enzyme that generates H3K9me3. Suv39h also interacts directly with HP1. However, the importance of HP1 interaction for Suv39h-mediated H3K9me3 formation at the pericentromere is not well characterized. To address this question, we introduced HP1 binding-defective, N-terminally truncated mouse Suv39h1 (ΔN) into Suv39h-deficient cells. Pericentric H3K9me3-positive cells were not detected by endogenous-level expression of ΔN. Notably, ΔN could induce pericentric accumulation of H3K9me3 as wild type Suv39h1 did if it was overexpressed. These findings demonstrate that the N-terminal region of Suv39h1, presumably via HP1-Suv39h1 interaction, is required for Suv39h1-mediated pericentric H3K9me3 formation, but can be overridden if Suv39h1 is overproduced, indicating that Suv39h1-mediated heterochromatin formation is controlled by multiple modules, including HP1.