SUZ12 is required for both the histone methyltransferase activity and the silencing function of the EED-EZH2 complex
SUZ12 is required for both the histone methyltransferase activity and the silencing function of the EED-EZH2 complex
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DOI：
10.1016/j.molcel.2004.06.020
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发表时间：
2004-07-02
期刊：
影响因子：
16
通讯作者：
Zhang, Y
中科院分区：
文献类型：
--
作者：
Cao, R;Zhang, Y
最近的研究揭示了EED-EZH 2复合物的内在组蛋白甲基转移酶（HMTase）活性及其在Hox基因沉默、X失活和癌症转移中的作用。在这项研究中，我们专注于单个组件的功能。我们发现HMTase活性需要至少三种组分-EZH 2，EED和SUZ 12-而AEBP 2是最佳酶活性所必需的。使用稳定的SUZ 12敲低细胞系，我们显示SUZ 12敲低导致细胞生长缺陷，这与H3-K27甲基化的全基因组改变以及许多Hox基因的上调相关。染色质免疫沉淀（ChIP）分析鉴定了位于HoxA 9转录起始位点上游4kb处的500 bp区域为SUZ 12结合位点，该区域响应SUZ 12敲低，并且可能在调节HoxA 9表达中起重要作用。因此，我们的研究确定了SUZ 12在H3-赖氨酸27甲基化和Hox基因沉默中的关键作用。
Recent studies have revealed the intrinsic histone methyltransferase [HMTase) activity of the EED-EZH2 complex and its role in Hox gene silencing, X inactivation, and cancer metastasis. In this study, we focus on the function of individual components. We found that the HMTase activity requires a minimum of three components-EZH2, EED, and SUZ12-while AEBP2 is required for optimal enzymatic activity. Using a stable SUZ12 knockdown cell line, we show SUZ12 knockdown results in cell growth defects, which correlate with genomo-wide alteration on H3-K27 methylation as well as upregulation of a number of Hox genes. Chromatin immunoprecipitation (ChIP) assay identified a 500 bp region located 4 kb upstream of the HoxA9 transcription initiation site as a SUZ12 binding site, which responds to SUZ12 knockdown and might play an important role in regulating HoxA9 expression. Thus, our study establishes a critical role of SUZ12 in H3-lysine 27 methylation and Hox gene silencing.