Distinctions in the specificity of E2F function revealed by gene expression signatures
Distinctions in the specificity of E2F function revealed by gene expression signatures
复制标题
DOI：
10.1073/pnas.0504300102
复制
发表时间：
2005-11-01
影响因子：
11.1
通讯作者：
Nevins, JR
中科院分区：
文献类型：
--
作者：
Black, EP;Hallstrom, T;Nevins, JR
E2F转录因子家族为协调细胞增殖和细胞命运的调控提供了必要的活性。E2F1和E2F3蛋白都被证明对细胞增殖特别重要，而E2F1蛋白具有促进细胞凋亡的能力。为了探索这种功能特异性的基础，我们使用DNA微阵列分析来探索这两种E2F活性的差异。区分E2F1或E2F3表达细胞与静止细胞的基因表达谱富含编码细胞周期和DNA复制活性的基因，这与许多过去的研究一致。E2F1基因图谱也丰富了已知的在细胞凋亡中起作用的基因。我们还确定了专门区分E2F1和E2F3活性的基因表达模式；这一图谱丰富了已知在有丝分裂中起作用的基因。E2F功能的特异性被归因于标记的BOX结构域介导的蛋白质相互作用，我们现在证明嵌合的E2F蛋白产生反映标记的BOX起源的表达信号，从而将功能特异性的生化机制与基因激活的特异性联系起来。
The E2F family of transcription factors provides essential activities for coordinating the control of cellular proliferation and cell fate. Both E2F1 and E2F3 proteins have been shown to be particularly important for cell proliferation, whereas the E2F1 protein has the capacity to promote apoptosis. To explore the basis for this specificity of function, we used DNA microarray analysis to probe for the distinctions in the two E2F activities. Gene expression profiles that distinguish either E2F1- or E2F3-expressing cells from quiescent cells are enriched in genes encoding cell cycle and DNA replication activities, consistent with many past studies. E2F1 profile is also enriched in genes known to function in apoptosis. We also identified patterns of gene expression that specifically differentiate the activity of E2F1 and E2F3; this profile is enriched in genes known to function in mitosis. The specificity of E2F function has been attributed to protein interactions mediated by the marked box domain, and we now show that chimeric E2F proteins generate expression signatures that reflect the origin of the marked box, thus linking the biochemical mechanism for specificity of function with specificity of gene activation.