Oktaba Katarzyna, Gutiérrez Luis, Gagneur Julien, Girardot Charles, Sengupta Aditya K, Furlong Eileen E M, Müller Jürg
EMBL, Gene Expression Programme, Heidelberg, Germany.
Dev Cell. 2008 Dec;15(6):877-89. doi: 10.1016/j.devcel.2008.10.005. Epub 2008 Nov 6.
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.
多梳蛋白组(PcG)蛋白形成保守的调控复合物,该复合物修饰染色质以抑制转录。在此,我们报告了PhoRC的全基因组结合图谱,PhoRC是果蝇的PcG蛋白复合物,包含DNA结合因子Pho/dYY1和dSfmbt。PhoRC在胚胎和幼虫中均持续占据大量发育调节基因的短多梳反应元件(PREs)。这些PREs中的大多数被PcG复合物PRC1和PRC2共同占据。对PcG突变体的分析表明,PcG系统抑制成虫盘前后、背腹和近端远端模式形成所需的基因,并且它还抑制细胞周期调节基因。这些基因中的许多以动态方式受到调控,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。对细胞周期调节因子的分析表明,PcG系统还动态调节某些基因的表达水平,这为PcG突变体的肿瘤表型提供了一种可能的解释。