Muramatsu Daisuke, Kimura Hiroshi, Kotoshiba Kaoru, Tachibana Makoto, Shinkai Yoichi
Graduate School of Biostudies, Kyoto University.
Cell Struct Funct. 2016 Dec 3;41(2):145-152. doi: 10.1247/csf.16013. Epub 2016 Oct 12.
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.
着丝粒周围区域形成表观遗传组织化的沉默异染色质结构，这些结构积累组蛋白H3赖氨酸9三甲基化（H3K9me3）和异染色质蛋白1（HP1），后者是一种与甲基化H3K9结合的蛋白。在着丝粒周围区域，Suv39h是产生H3K9me3的主要酶。Suv39h还直接与HP1相互作用。然而，HP1相互作用对着丝粒处Suv39h介导的H3K9me3形成的重要性尚未得到充分表征。为了解决这个问题，我们将HP1结合缺陷型、N端截短的小鼠Suv39h1（ΔN）导入Suv39h缺陷细胞中。通过ΔN的内源水平表达未检测到着丝粒周围H3K9me3阳性细胞。值得注意的是，如果ΔN过表达，它可以像野生型Suv39h1一样诱导H3K9me3在着丝粒周围积累。这些发现表明，Suv39h1的N端区域可能通过HP1-Suv39h1相互作用，是Suv39h1介导的着丝粒周围H3K9me3形成所必需的，但如果Suv39h1过量产生则可以被克服，这表明Suv39h1介导的异染色质形成受包括HP1在内的多个模块控制。
