多梳蛋白Cbx4促进从头DNA甲基转移酶Dnmt3a的SUMO修饰。
Polycomb protein Cbx4 promotes SUMO modification of de novo DNA methyltransferase Dnmt3a.
作者信息
Li Bing, Zhou Jing, Liu Peng, Hu Jialei, Jin Hong, Shimono Yohei, Takahashi Masahide, Xu Guoliang
机构信息
State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, People's Republic of China.
出版信息
Biochem J. 2007 Jul 15;405(2):369-78. doi: 10.1042/BJ20061873.
The 'de novo methyltransferase' Dnmt3a (DNA methyltransferase 3a) has been shown to mediate transcriptional repression. Post-translational modification of Dnmt3a by SUMOylation affects its ability to transcriptionally repress. However, very little is known about how the SUMOylation process is regulated. In the present study, we identified a PcG (Polycomb group) protein, Cbx4 (chromobox 4), as a specific interaction partner of Dnmt3a. Co-expression of Cbx4 and SUMO-1 (small ubiquitin-related modifier-1) along with Dnmt3a in transfected cells results in enhanced modification of Dnmt3a with SUMO-1. Purified Cbx4 also promotes SUMOylation of Dnmt3a in vitro. The modification occurs in the N-terminal regulatory region, including the PWWP (Pro-Trp-Trp-Pro) domain. Our results suggest that Cbx4 functions as a SUMO E3 ligase for Dnmt3a and it might be involved in the functional regulation of DNA methyltransferases by promoting their SUMO modification.
“从头甲基转移酶”Dnmt3a（DNA甲基转移酶3a）已被证明可介导转录抑制。SUMO化对Dnmt3a进行的翻译后修饰会影响其转录抑制能力。然而，关于SUMO化过程如何被调控却知之甚少。在本研究中，我们鉴定出一种多梳蛋白组（PcG）蛋白Cbx4（染色体框蛋白4），它是Dnmt3a的特异性相互作用伴侣。在转染细胞中，Cbx4、SUMO-1（小泛素相关修饰物-1）与Dnmt3a共表达会增强Dnmt3a的SUMO-1修饰。纯化的Cbx4在体外也能促进Dnmt3a的SUMO化。这种修饰发生在包括PWWP（脯氨酸-色氨酸-色氨酸-脯氨酸）结构域在内的N端调控区域。我们的结果表明，Cbx4作为Dnmt3a的SUMO E3连接酶发挥作用，并且它可能通过促进DNA甲基转移酶的SUMO修饰参与其功能调控。
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