Oktyabri Dulamsuren, Tange Shoichiro, Terashima Minoru, Ishimura Akihiko, Suzuki Takeshi
Division of Functional Genomics, Cancer Research Institute, Kanazawa University, Kanazawa 920-1192, Ishikawa, Japan.
Division of Functional Genomics, Cancer Research Institute, Kanazawa University, Kanazawa 920-1192, Ishikawa, Japan.
Biochem Biophys Res Commun. 2014 Oct 10;453(1):124-30. doi: 10.1016/j.bbrc.2014.09.082. Epub 2014 Sep 26.
Histone methylation is involved in various biological and pathological processes including cancer development. In this study, we found that EED, a component of Polycomb repressive complex-2 (PRC2) that catalyzes methylation of lysine 27 of histone H3 (H3K27), was involved in epithelial-mesenchymal transition (EMT) of cancer cells induced by Transforming Growth Factor-beta (TGF-β). The expression of EED was increased during TGF-β-induced EMT and knockdown of EED inhibited TGF-β-induced morphological conversion of the cells associated with EMT. EED knockdown antagonized TGF-β-dependent expression changes of EMT-related genes such as CDH1, ZEB1, ZEB2 and microRNA-200 (miR-200) family. Chromatin immunoprecipitation assays showed that EED was implicated in TGF-β-induced transcriptional repression of CDH1 and miR-200 family genes through the regulation of histone H3 methylation and EZH2 occupancies on their regulatory regions. Our study demonstrated a novel role of EED, which regulates PRC2 activity and histone methylation during TGF-β-induced EMT of cancer cells.
组蛋白甲基化参与包括癌症发展在内的各种生物学和病理过程。在本研究中，我们发现EED是多梳抑制复合物2（PRC2）的一个组成部分，可催化组蛋白H3赖氨酸27（H3K27）的甲基化，它参与了由转化生长因子-β（TGF-β）诱导的癌细胞上皮-间质转化（EMT）。在TGF-β诱导的EMT过程中，EED的表达增加，敲低EED可抑制TGF-β诱导的与EMT相关的细胞形态转化。敲低EED可拮抗TGF-β依赖的EMT相关基因如CDH1、ZEB1、ZEB2和微小RNA-200（miR-200）家族的表达变化。染色质免疫沉淀分析表明，EED通过调节组蛋白H3甲基化以及EZH2在其调控区域的占据情况，参与了TGF-β诱导的CDH1和miR-200家族基因的转录抑制。我们的研究证明了EED的一个新作用，即在TGF-β诱导的癌细胞EMT过程中调节PRC2活性和组蛋白甲基化。
