The HDAC-Associated Sin3B Protein Represses DREAM Complex Targets and Cooperates with APC/C to Promote Quiescence
The HDAC-Associated Sin3B Protein Represses DREAM Complex Targets and Cooperates with APC/C to Promote Quiescence
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DOI：
10.1016/j.celrep.2018.11.024
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发表时间：
2018-12-04
期刊：
影响因子：
8.8
通讯作者：
David, Gregory
中科院分区：
文献类型：
--
作者：
Bainor, Anthony J.;Saini, Siddharth;David, Gregory
哺乳动物的DREAM复合体负责数百个细胞周期相关基因在静止期的转录抑制。梦复合体如何招募染色质修饰实体来帮助其抑制仍然是未知的。使用无偏见的蛋白质组学分析，我们已经发现了一个强大的染色质相关的Sin 3B蛋白和DREAM复合物之间的关联。我们已经确定，Sin 3B的基因失活导致DREAM靶基因在静止期的去抑制，但不足以让静止细胞恢复增殖。然而，APC/C-CDH 1的失活足以使Sin 3B（-/-）细胞而不是亲本细胞重新进入细胞周期。这些研究确定Sin 3B作为一个转录辅阻遏物与DREAM复合物在静止期，并揭示了E2 F靶抑制和APC/C-CDH 1在细胞周期进程的负调控功能之间的合作。
The mammalian DREAM complex is responsible for the transcriptional repression of hundreds of cell-cycle-related genes in quiescence. How the DREAM complex recruits chromatin-modifying entities to aid in its repression remains unknown. Using unbiased proteomics analysis, we have uncovered a robust association between the chromatin-associated Sin3B protein and the DREAM complex. We have determined that genetic inactivation of Sin3B results in the de-repression of DREAM target genes during quiescence but is insufficient to allow quiescent cells to resume proliferation. However, inactivation of APC/C-CDH1 was sufficient for Sin3B(-/-) cells, but not parental cells, to re-enter the cell cycle. These studies identify Sin3B as a transcriptional corepressor associated with the DREAM complex in quiescence and reveals a functional cooperation between E2F target repression and APC/C-CDH1 in the negative regulation of cell-cycle progression.