dREAM/MMB 复合物在分化特异性 E2F/RB 靶基因调控中的双重作用。
A dual role for the dREAM/MMB complex in the regulation of differentiation-specific E2F/RB target genes.
机构信息
Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey, USA.
出版信息
Mol Cell Biol. 2012 Jun;32(11):2110-20. doi: 10.1128/MCB.06314-11. Epub 2012 Mar 26.
Abstract
E2F and RB proteins regulate the expression of genes involved in cell cycle progression, apoptosis, differentiation, and development. Recent studies indicate that they function as part of an evolutionarily conserved multiprotein complex termed dREAM/DREAM/LINC. Here we characterize the role of the Drosophila complex, dREAM, in the regulation of differentiation-specific E2F target genes in actively proliferating cells. These genes are regulated differently from cell cycle-related E2F targets, they do not depend on E2F activation, and E2F/RB repression is maintained throughout the cell cycle. In proliferating cells, their repression is dependent on dREAM. We find that dREAM plays a dual role in their regulation. First, it is required for the stability of the repressive dE2F2/RBF complexes at their promoters during S phase. Second, we find that dREAM is indispensable for both transcriptional repression mechanisms employed at these genes.
摘要
E2F 和 RB 蛋白调节细胞周期进程、细胞凋亡、分化和发育相关基因的表达。最近的研究表明，它们作为一个进化上保守的多蛋白复合物的一部分发挥作用，该复合物称为 dREAM/DREAM/LINC。在这里，我们描述了果蝇复合物 dREAM 在调节活跃增殖细胞中分化特异性 E2F 靶基因中的作用。这些基因的调控不同于细胞周期相关的 E2F 靶基因，它们不依赖于 E2F 激活，并且 E2F/RB 抑制在整个细胞周期中都得以维持。在增殖细胞中，它们的抑制依赖于 dREAM。我们发现 dREAM 在它们的调节中发挥双重作用。首先，它在 S 期期间在其启动子处稳定抑制性 dE2F2/RBF 复合物是必需的。其次，我们发现 dREAM 对于这些基因所采用的两种转录抑制机制都是不可或缺的。
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