Pocket protein complexes are recruited to distinct targets in quiescent and proliferating cells
Pocket protein complexes are recruited to distinct targets in quiescent and proliferating cells
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DOI：
10.1128/mcb.25.18.8166-8178.2005
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发表时间：
2005-09-01
影响因子：
5.3
通讯作者：
Dynlacht, BD
中科院分区：
文献类型：
--
作者：
Balciunaite, E;Spektor, A;Dynlacht, BD
生物化学和遗传学研究已经确定视网膜母细胞瘤蛋白（pRB）肿瘤抑制因子家族成员具有重叠的功能。然而，这些研究在很大程度上未能区分高度相关的p107和p130蛋白之间的功能差异。此外，大多数关于pRB家族及其主要靶点E2F转录因子的研究都集中在从静止状态重新启动细胞周期的细胞上，尽管最近的研究表明，循环细胞表现出与促有丝分裂刺激细胞不同的调节层。使用全基因组染色质免疫沉淀，我们发现，有不同类别的基因直接调控E2F4，p107，和p130的独特组合，包括一组基因在细胞周期中的具体调控。这些群体表现出不同的组蛋白乙酰化签名和哺乳动物Sin3B辅阻遏物募集模式。我们的研究结果表明，细胞周期依赖性抑制的结果从一个意想不到的阵列的不同复合物的招聘，并揭示了特定的差异，在循环和静止细胞的转录调控。此外，因子定位分析，第一次，允许识别的高度相关的转录调节因子p107和p130的新的和特定的目标，这表明新的和不同的监管网络从事每种蛋白质在连续循环的细胞。
Biochemical and genetic studies have determined that retinoblastoma protein (pRB) tumor suppressor family members have overlapping functions. However, these studies have largely failed to distinguish functional differences between the highly related p107 and p130 proteins. Moreover, most studies pertaining to the pRB family and its principal target, the E2F transcription factor, have focused on cells that have reinitiated a cell cycle from quiescence, although recent studies suggest that cycling cells exhibit layers of regulation distinct from mitogenically stimulated cells. Using genome-wide chromatin immunoprecipitation, we show that there are distinct classes of genes directly regulated by unique combinations of E2F4, p107, and p130, including a group of genes specifically regulated in cycling cells. These groups exhibit both distinct histone acetylation signatures and patterns of mammalian Sin3B corepressor recruitment. Our findings suggest that cell cycledependent repression results from recruitment of an unexpected array of diverse complexes and reveals specific differences between transcriptional regulation in cycling and quiescent cells. In addition, factor location analyses have, for the first time, allowed the identification of novel and specific targets of the highly related transcriptional regulators p107 and p130, suggesting new and distinct regulatory networks engaged by each protein in continuously cycling cells.