The CTCF Insulator Protein Is Posttranslationally Modified by SUMO
The CTCF Insulator Protein Is Posttranslationally Modified by SUMO
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DOI：
10.1128/mcb.00825-08
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发表时间：
2009-02-01
影响因子：
5.3
通讯作者：
Sadowski, Paul D.
中科院分区：
文献类型：
--
作者：
MacPherson, Melissa J.;Beatty, Linda G.;Sadowski, Paul D.
CTCF蛋白是一种高度保守的锌指蛋白，参与基因调控和核组织的许多方面。它的功能包括作为基因的抑制因子，包括c-myc癌基因。在本文中，我们发现CTCF蛋白可以被小的泛素样蛋白SUMO翻译后修饰。CTCF在体内和体外都被SUMOylation，我们在蛋白质中确定了两个主要的SUMOylation位点。SUMO蛋白对CTCF的翻译后修饰并不影响其在体外与DNA结合的能力。CTCF的sumo化有助于CTCF对c-myc P2启动子的抑制作用。我们还发现CTCF和抑制Polycomb蛋白Pc2共定位于核Polycomb小体。Pc2蛋白可能作为CTCF的SUMO E3连接酶，强烈增强了SUMO 2和3对CTCF的修饰。这些研究扩大了CTCF翻译后修饰的范围，并提出了这些修饰在其调控表观遗传状态中的作用。
The CTCF protein is a highly conserved zinc finger protein that is implicated in many aspects of gene regulation and nuclear organization. Its functions include the ability to act as a repressor of genes, including the c-myc oncogene. In this paper, we show that the CTCF protein can be posttranslationally modified by the small ubiquitin-like protein SUMO. CTCF is SUMOylated both in vivo and in vitro, and we identify two major sites of SUMOylation in the protein. The posttranslational modification of CTCF by the SUMO proteins does not affect its ability to bind to DNA in vitro. SUMOylation of CTCF contributes to the repressive function of CTCF on the c-myc P2 promoter. We also found that CTCF and the repressive Polycomb protein, Pc2, are colocalized to nuclear Polycomb bodies. The Pc2 protein may act as a SUMO E3 ligase for CTCF, strongly enhancing its modification by SUMO 2 and 3. These studies expand the repertoire of posttranslational modifications of CTCF and suggest roles for such modifications in its regulation of epigenetic states.