Involvement of SUMO modification in MBD1- and MCAF1-mediated heterochromatin formation
Involvement of SUMO modification in MBD1- and MCAF1-mediated heterochromatin formation
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DOI：
10.1074/jbc.m602280200
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发表时间：
2006-08-11
影响因子：
4.8
通讯作者：
Saitoh, Hisato
中科院分区：
文献类型：
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作者：
Uchimura, Yasuhiro;Ichimura, Takaya;Saitoh, Hisato
与泛素相关的小分子修饰物SUMO-2/3和SUMO-1参与基因调控和核结构。然而，关于相扑在哺乳动物细胞异染色质形成中的作用，人们知之甚少。在这里，我们证明了SUMOS直接与人MCAF1相互作用，MCAF1与甲基CpG结合蛋白MBD1或SETDB1形成复合物，在MCAF1存在下，组蛋白H3在赖氨酸9(H3-K9)上三甲基化。用SUMO-2/3或SUMO-1修饰MBD1促进了MBD1和MCAF1之间的相互作用，这表明SUMO化连接了DNA和组蛋白的甲基化。在培养的人细胞系中，SUMOS定位于含有MBD1和MCAF1的异染色质区域，这些区域富含三甲基-H3-K9以及异染色质蛋白HP1β和HP1伽马。SUMO-2/3或SUMO-1的特异性敲除导致MCAF1、三甲基-H3-K9和HP1蛋白从含有MBD1的异染色质焦点上解离，这表明需要SUMO进行异染色质组装。这些发现为SUMO化在调节异染色质形成和基因沉默中的作用提供了洞察力。
Small ubiquitin-related modifiers, SUMO-2/3 and SUMO-1, are involved in gene regulation and nuclear structures. However, little is known about the roles of SUMO, in heterochromatin formation of mammalian cells. Here we demonstrate that SUMOs directly interact with human MCAF1, which forms complexes with either the methyl-CpG-binding protein MBD1 or SETDB1, which trimethylates histone H3 at lysine 9 (H3-K9) in the presence of MCAF1. Modification of MBD1 with either SUMO-2/3 or SUMO-1 facilitated the interaction between MBD1 and MCAF1, suggesting that SUMOylation links the methylation of DNA and histones. In a cultured human cell line, SUMOs were localized in MBD1- and MCAF1-containing heterochromatin regions that were enriched in trimethyl-H3-K9 and the heterochromatin proteins HP1 beta and HP1 gamma. Specific knockdown of either SUMO-2/3 or SUMO-1 induced dissociation of MCAF1, trimethyl-H3-K9, and the HP1 proteins from the MBD1-containing heterochromatin foci, suggesting a requirement for SUMOs for heterochromatin assembly. These findings provide insights into the roles of SUMOylation in the regulation of heterochromatin formation and gene silencing.