LIN54 is an essential core subunit of the DREAM/LINC complex that binds to the cdc2 promoter in a sequence-specific manner
LIN54 is an essential core subunit of the DREAM/LINC complex that binds to the cdc2 promoter in a sequence-specific manner
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DOI：
10.1111/j.1742-4658.2009.07261.x
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发表时间：
2009-10-01
期刊：
影响因子：
5.4
通讯作者：
Gaubatz, Stefan
中科院分区：
文献类型：
--
作者：
Schmit, Fabienne;Cremer, Sarah;Gaubatz, Stefan
最近，保守的人类LINC/DREAM复合物已被描述为细胞周期基因的重要调控因子。LINC由一个核心模块组成，该模块以细胞周期依赖性方式动态地与E2 F转录因子、p130和B-MYB转录因子相关联。在这项研究中，我们分析了LINC的进化保守的LIN 54亚基。我们发现LIN 54是细胞周期进程所必需的。蛋白质相互作用研究表明，预测的螺旋-卷曲-螺旋基序是LIN 54与p130和B-MYB相互作用所必需的。此外，我们发现LIN 54的富含半胱氨酸的CXC结构域是一种新的DNA结合结构域，其以序列特异性方式结合cdc 2启动子。我们确定了两个结合位点的LIN 54在cdc 2启动子，其中之一重叠的细胞周期同源区域的转录起始位点。凝胶迁移试验表明，在静止细胞中，LIN 54在细胞周期同源区的结合是通过E2 F4与相邻细胞周期依赖性元件的结合来稳定的。我们的数据表明，LIN 54是LINC的一个重要的和完整的亚基。
Recently, the conserved human LINC/DREAM complex has been described as an important regulator of cell cycle genes. LINC consists of a core module that dynamically associates with E2F transcription factors, p130 and the B-MYB transcription factor in a cell cycle-dependent manner. In this study, we analyzed the evolutionary conserved LIN54 subunit of LINC. We found that LIN54 is required for cell cycle progression. Protein interaction studies demonstrated that a predicted helix-coil-helix motif is required for the interaction of LIN54 with p130 and B-MYB. In addition, we found that the cysteine-rich CXC domain of LIN54 is a novel DNA-binding domain that binds to the cdc2 promoter in a sequence-specific manner. We identified two binding sites for LIN54 in the cdc2 promoter, one of which overlaps with the cell cycle homology region at the transcriptional start site. Gel shift assays suggested that, in quiescent cells, the binding of LIN54 at the cell cycle homology region is stabilized by the binding of E2F4 to the adjacent cell cycle-dependent element. Our data demonstrate that LIN54 is an important and integral subunit of LINC.