Schmit Fabienne, Korenjak Michael, Mannefeld Mirijam, Schmitt Kathrin, Franke Claudia, von Eyss Björn, Gagrica Sladjana, Hänel Frank, Brehm Alexander, Gaubatz Stefan
Department of Physiological Chemistry I, Biocenter, University of Würzburg, Würzburg, Germany.
Cell Cycle. 2007 Aug 1;6(15):1903-13. doi: 10.4161/cc.6.15.4512. Epub 2007 May 25.
Here we report the identification of the LIN complex (LINC), a human multiprotein complex that is required for transcriptional activation of G2/M genes. LINC is related to the recently identified dREAM and DRM complexes of Drosophila and C. elegans that contain homologs of the mammalian retinoblastoma tumor suppressor protein. The LINC core complex consists of at least five subunits including the chromatin-associated LIN-9 and RbAp48 proteins. LINC dynamically associates with pocket proteins, E2F and B-MYB during the cell cycle. In quiescent cells, LINC binds to p130 and E2F4. During cell cycle entry, E2F4 and p130 dissociate and LINC switches to B-MYB and p107. Chromatin Immunoprecipitation experiments demonstrate that LINC associates with a large number of E2F-regulated promoters in quiescent cells. However, RNAi experiments reveal that LINC is not required for repression. In S-phase, LINC selectively binds to the promoters of G2/M genes whose products are required for mitosis and plays an important role in their cell cycle dependent activation.
在此，我们报告了LIN复合物（LINC）的鉴定，它是一种人类多蛋白复合物，是G2/M期基因转录激活所必需的。LINC与最近在果蝇和秀丽隐杆线虫中鉴定出的dREAM和DRM复合物相关，这些复合物包含哺乳动物视网膜母细胞瘤肿瘤抑制蛋白的同源物。LINC核心复合物至少由五个亚基组成，包括与染色质相关的LIN-9和RbAp48蛋白。在细胞周期中，LINC与口袋蛋白、E2F和B-MYB动态结合。在静止细胞中，LINC与p130和E2F4结合。在细胞周期进入时，E2F4和p130解离，LINC转而与B-MYB和p107结合。染色质免疫沉淀实验表明，LINC在静止细胞中与大量E2F调控的启动子相关联。然而，RNA干扰实验表明，LINC对于抑制作用并非必需。在S期，LINC选择性地结合G2/M期基因的启动子，这些基因的产物是有丝分裂所必需的，并且在其细胞周期依赖性激活中起重要作用。
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