The ZNF217 oncogene is a candidate organizer of repressive histone modifiers.
The ZNF217 oncogene is a candidate organizer of repressive histone modifiers.
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DOI：
10.4161/epi.4.2.7953
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发表时间：
2009-02-16
期刊：
影响因子：
3.7
通讯作者：
Walsh MJ
中科院分区：
文献类型：
--
作者：
Banck MS;Li S;Nishio H;Wang C;Beutler AS;Walsh MJ
锌指蛋白217（ZNF 217）是一种重要的癌基因，在许多癌症类型中的高频率扩增和过表达，但其基因调控的分子模式知之甚少。我们通过亲和层析纯化了ZNF 217核结合蛋白复合物，并通过质谱鉴定其组分为Jarid 1b/Plu-1，G9 a，LSD 1，CoREST和CtBP 1。这些与ZNF 217的单独结合通过共免疫印迹（IP）确认。这些蛋白质的已知活性表明ZNF 217复合物在组蛋白修饰中的作用。使用体外试验证明了以下活性：组蛋白H3赖氨酸4三甲基（H3 K4 me 3）脱甲基酶活性，其在阴离子交换色谱中与Jarid 1b/Plu-1共分级; H3 K9甲基化，G9 a的已知主要活性;和H3 K27甲基化。后者表明EZH 2是另一种ZNF 217结合候选物，这可以通过co-IP来证实。综上所述，这些发现表明ZNF 217在靶DNA位点组装了一组独特的组蛋白修饰蛋白，在转录抑制中协同作用。
The zinc finger protein 217 (ZNF217) is an important oncogene based on the high frequency of amplification and overexpression in many cancer types, but its molecular mode of gene regulation is poorly understood. We purified a complex of nuclear ZNF217-binding proteins by affinity chromatography and identified its components by mass spectrometry as Jarid1b/Plu-1, G9a, LSD1, CoREST and CtBP1. Individual binding of these with ZNF217 was confirmed by co-immunoprecipiation (IP). Known activities of these proteins suggested a role of the ZNF217 complex in histone modification. Using in vitro assays the following activities were demonstrated: Histone H3 lysine 4 trimethyl (H3K4me3) demethylase activity, which co-fractionated with Jarid1b/Plu-1 in anion-exchange chromatography; H3K9 methylation, the known principal activity of G9a; and H3K27 methylation. The latter suggested EZH2 as another ZNF217 binding candidate, which could be confirmed by co-IP. Taken together, these findings suggest that ZNF217 assembles a distinct set of histone modifying proteins at target DNA sites that act synergistically in transcriptional repression.
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