Dynamic Regulation by Polycomb Group Protein Complexes Controls Pattern Formation and the Cell Cycle in Drosophila

Dynamic Regulation by Polycomb Group Protein Complexes Controls Pattern Formation and the Cell Cycle in Drosophila
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DOI:
10.1016/j.devcel.2008.10.005
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发表时间:
2008-12-09
期刊:
影响因子:
11.8
通讯作者:
Mueller, Juerg
Mueller, Juerg
中科院分区:
生物学1区
文献类型:
--
作者:
Oktaba, Katarzyna;Gutierrez, Luis;Mueller, Juerg

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多梳组(PcG)蛋白形成保守的调节复合物,其修饰染色质以抑制转录。在这里,我们报告全基因组的PhoRC,果蝇PcG蛋白复合物含有DNA结合因子Pho/dYY 1和dSfmbt的结合概况。PhoRC在胚胎和幼虫中组成性地占据了大量发育调节基因的短Polycomb响应元件(PREs)。这些PRE中的大多数被PcG复合物PRC 1和PRC 2共同占据。PcG突变体的分析表明,PcG系统抑制基因所需的前后,背腹,和proximodistal图案的成虫盘,它也抑制细胞周期调节基因。其中许多基因以动态方式受到调节,我们的结果表明PcG系统将信号介导的靶基因激活限制在适当的细胞中。细胞周期调节因子的分析表明,PcG系统也动态地调节某些基因的表达水平,为PcG突变体的肿瘤表型提供了一个可能的解释。
Polycomb group (PcG) proteins form conserved regulatory complexes that modify chromatin to repress transcription. Here, we report genome-wide binding profiles of PhoRC, the Drosophila PcG protein complex containing the DNA-binding factor Pho/dYY1 and dSfmbt. PhoRC constitutively occupies short Polycomb response elements (PREs) of a large set of developmental regulator genes in both embryos and larvae. The majority of these PREs are co-occupied by the PcG complexes PRC1 and PRC2. Analysis of PcG mutants shows that the PcG system represses genes required for anteroposterior, dorsoventral, and proximodistal patterning of imaginal discs and that it also represses cell cycle regulator genes. Many of these genes are regulated in a dynamic manner, and our results suggest that the PcG system restricts signaling-mediated activation of target genes to appropriate cells. Analysis of cell cycle regulators indicates that the PcG system also dynamically modulates the expression levels of certain genes, providing a possible explanation for the tumor phenotype of PcG mutants.