Zhou Jing, Wang Qiaoqiao, Chen Ling-Ling, Carmichael Gordon G
Department of Genetics and Developmental Biology, University of Connecticut Stem Cell Institute, University of Connecticut Health Center, Farmington, Connecticut 06030-3301, USA
RNA. 2008 Sep;14(9):1773-81. doi: 10.1261/rna.1036308. Epub 2008 Jul 22.
Vigilin is an RNA-binding protein localized to both the cytoplasm and the nucleus and has been previously implicated in heterochromatin formation and chromosome segregation. We demonstrate here that the C-terminal domain of human vigilin binds to the histone methyltransferase SUV39H1 in vivo. This association is independent of RNA and maps to a site on vigilin that is not involved in its interaction with several other known protein partners. Cells that express high levels of the C-terminal fragment display chromosome segregation defects, and ChIP analyses show changes in the status of pericentric beta-satellite and rDNA chromatin from heterochromatic to more euchromatic form. Finally, a cell line with inducible expression of the vigilin C-terminal fragment displays inducible alterations in beta-satellite chromatin. These and other results lead us to present a new model for vigilin-mediated, RNA-induced gene silencing.
vigilin是一种RNA结合蛋白，定位于细胞质和细胞核，先前已被证明与异染色质形成和染色体分离有关。我们在此证明，人类vigilin的C末端结构域在体内与组蛋白甲基转移酶SUV39H1结合。这种关联不依赖于RNA，且定位于vigilin上一个不参与其与其他几个已知蛋白质伙伴相互作用的位点。表达高水平C末端片段的细胞表现出染色体分离缺陷，染色质免疫沉淀分析显示，着丝粒周围β卫星和核糖体DNA染色质的状态从异染色质形式转变为更开放的常染色质形式。最后，一个可诱导表达vigilin C末端片段的细胞系在β卫星染色质中表现出可诱导的变化。这些以及其他结果使我们提出了一个关于vigilin介导的、RNA诱导的基因沉默的新模型。
