Guenatri Mounia, Bailly Delphine, Maison Christèle, Almouzni Geneviève
Institut Curie/Research section, UMR218 du Centre National pour la Recherche Scientifique, 26 rue d'Ulm, 75248 Paris Cedex 05, France.
J Cell Biol. 2004 Aug 16;166(4):493-505. doi: 10.1083/jcb.200403109. Epub 2004 Aug 9.
Heterochromatin is thought to play a critical role for centromeric function. However, the respective contributions of the distinct repetitive sequences found in these regions, such as minor and major satellites in the mouse, have remained largely unsolved. We show that these centric and pericentric repeats on the chromosomes have distinct heterochromatic characteristics in the nucleus. Major satellites from different chromosomes form clusters associated with heterochromatin protein 1alpha, whereas minor satellites are individual entities associated with centromeric proteins. Both regions contain methylated histone H3 (Me-K9 H3) but show different micrococcal nuclease sensitivities. A dinucleosome repeating unit is found specifically associated with major satellites. These domains replicate asynchronously, and chromatid cohesion is sustained for a longer time in major satellites compared with minor satellites. Such prolonged cohesion in major satellites is lost in the absence of Suv39h histone methyltransferases. Thus, we define functionally independent centromeric subdomains, which spatio-temporal isolation is proposed to be important for centromeric cohesion and dissociation during chromosome segregation.
异染色质被认为在着丝粒功能中起关键作用。然而,这些区域中发现的不同重复序列(如小鼠中的小卫星和大卫星)各自的贡献在很大程度上仍未解决。我们表明,染色体上的这些着丝粒和近着丝粒重复序列在细胞核中具有不同的异染色质特征。来自不同染色体的大卫星形成与异染色质蛋白1α相关的簇,而小卫星是与着丝粒蛋白相关的单个实体。这两个区域都含有甲基化组蛋白H3(Me-K9 H3),但显示出不同的微球菌核酸酶敏感性。发现一个双核小体重复单元与大卫星特异性相关。这些结构域异步复制,与小卫星相比,大卫星中的染色单体凝聚持续时间更长。在没有Suv39h组蛋白甲基转移酶的情况下,大卫星中这种延长的凝聚会丧失。因此,我们定义了功能上独立的着丝粒亚结构域,其时空隔离被认为对染色体分离过程中的着丝粒凝聚和解离很重要。