A family of human zinc finger proteins that bind methylated DNA and repress transcription
A family of human zinc finger proteins that bind methylated DNA and repress transcription
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DOI：
10.1128/mcb.26.1.169-181.2006
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发表时间：
2006-01-01
影响因子：
5.3
通讯作者：
Defossez, PA
中科院分区：
文献类型：
--
作者：
Filion, GJP;Zhenilo, S;Defossez, PA
在脊椎动物中，DNA高度甲基化与非活跃转录有关。这个过程中的参与者包括MBD家族的蛋白质，它们可以识别甲基化的CPGS并抑制转录。Kaiso是一种结构无关的蛋白质，也被证明通过其三个类似Kruppel的C2H2锌指与甲基化的CGCG结合。人类基因组包含两种未鉴定的蛋白质，ZBTB4和ZBTB38，它们含有类似Kaiso的锌指。我们报道了ZBTB4和ZBTB38在体外和体内结合甲基化的DNA。与Kaiso不同的是，它们可以结合单个甲基化的CPGS。当在小鼠细胞中转染时，这些蛋白与高度甲基化的卫星DNA的焦点共同定位，并在DNA甲基化缺失时变得非定位。染色质免疫沉淀表明，这两种蛋白都与H19/Igf2差异甲基化区域的甲基化等位基因特异结合。ZBTB4和ZBTB38在转染实验中抑制甲基化模板的转录。这两个基因有不同的组织特异性表达模式，但都在大脑中高度表达。我们的结果揭示了存在一个与甲基化的CPGS结合的Kaiso样蛋白家族。与MBD家族的蛋白质一样，它们能够以甲基依赖的方式抑制转录，但它们的组织特异性表达模式表明功能不重叠。
In vertebrates, densely methylated DNA is associated with inactive transcription. Actors in this process include proteins of the MBD family that can recognize methylated CpGs and repress transcription. Kaiso, a structurally unrelated protein, has also been shown to bind methylated CGCGs through its three Kruppel-like C2H2 zinc fingers. The human genome contains two uncharacterized proteins, ZBTB4 and ZBTB38, that contain Kaiso-like zinc fingers. We report that ZBTB4 and ZBTB38 bind methylated DNA in vitro and in vivo. Unlike Kaiso, they can bind single methylated CpGs. When transfected in mouse cells, the proteins colocalize with foci of heavily methylated satellite DNA and become delocalized upon loss of DNA methylation. Chromatin immunoprecipitation suggests that both of these proteins specifically bind to the methylated allele of the H19/Igf2 differentially methylated region. ZBTB4 and ZBTB38 repress the transcription of methylated templates in transfection assays. The two genes have distinct tissue-specific expression patterns, but both are highly expressed in the brain. Our results reveal the existence of a family of Kaiso-like proteins that bind methylated CpGs. Like proteins of the MBD family, they are able to repress transcription in a methyl-dependent manner, yet their tissue-specific expression pattern suggests nonoverlapping functions.