Guarda Alessia, Bolognese Fabrizio, Bonapace Ian Marc, Badaracco Gianfranco
Department of Structural and Functional Biology, University of Insubria, via Alberto da Giussano 12, Busto Arsizio (VA), Italy.
Exp Cell Res. 2009 Jul 1;315(11):1895-903. doi: 10.1016/j.yexcr.2009.01.019. Epub 2009 Feb 2.
The nuclear membrane has an important role for the dynamic regulation of the genome, besides the well-established cytoskeletal function. The nuclear lamina is emerging as an important player in the organization of the position and functional state of interphase chromosomes. Epigenetic modifications such as DNA methylation and histone modifications are required for genome reprogramming during development, tissue-specific gene expression and global gene silencing. The Methyl-CpG binding protein MeCP2 binds methyl-CpG dinucleotides in the mammalian genome and functions as a transcriptional repressor in vivo by interacting with Sin3A, thereby recruiting histone deacetylases (HDAC). MeCP2 also mediates the formation of higher-order chromatin structures contributing to determine the architectural organization of the nucleus. In this paper, we show that MeCP2 interacts in vitro and in vivo with the inner nuclear membrane protein LBR and that the unstructured aminoacidic sequence linking the MBD and TRD domains of MeCP2 is responsible for this association. The formation of an LBR-MeCP2 protein complex might help providing a molecular explanation to the distribution of part of the heterochromatin at the nuclear periphery linked to inner membrane.
除了已确定的细胞骨架功能外，核膜在基因组的动态调控中也起着重要作用。核纤层蛋白正成为间期染色体位置和功能状态组织中的重要参与者。DNA甲基化和组蛋白修饰等表观遗传修饰是发育过程中基因组重编程、组织特异性基因表达和全局基因沉默所必需的。甲基化CpG结合蛋白MeCP2在哺乳动物基因组中结合甲基化CpG二核苷酸，并通过与Sin3A相互作用在体内作为转录抑制因子发挥作用，从而募集组蛋白脱乙酰酶（HDAC）。MeCP2还介导高阶染色质结构的形成，有助于确定细胞核的结构组织。在本文中，我们表明MeCP2在体外和体内与内核膜蛋白LBR相互作用，并且连接MeCP2的MBD和TRD结构域的无结构氨基酸序列负责这种关联。LBR-MeCP2蛋白复合物的形成可能有助于为与内膜相连的核周边部分异染色质的分布提供分子解释。
