欧洲分子生物学实验所位于德国汉堡的表观基因研究项目组和发育生物学项目组的科学家以果蝇为研究模型,揭示复杂的Polycomb Group Protein Complexes对细胞形成和细胞分裂模式的动力控制机制。相关文章发表在11月6日Cell子刊Development Cell在线版上。
Polycomb Group(PcG )蛋白形成保守的调控复合物,对染色质的表达转录具有修饰作用。研究小组从整个基因组范围以及相关的结合蛋白PhoRC研究果蝇的PcG蛋白复合物,包括其中的DNA结合因子Pho/dYY1和dSfmbt。在果蝇胚胎与幼虫发育阶段,PhoRC构成短调节基因表达的Polycomb效应元素(short Polycomb response elements,PREs)。
PREs与PcG复合物PRC1和PRC2共同出现。对PcG突变体研究发现,PcG系统表达基因在幼虫发育的前端、背腹以及远端模式都是必须的,同时可抑制细胞分裂调节基因的活性。大量的基因群以动态的调节模式工作,研究小组的研究结果表明,PcG系统限制部分细胞的信号介导的靶基因活性。对细胞分裂调节研究发现,PcG系统在某些基因表达的模式上是以动态的形式进行的,这为研究肿瘤的PcG突变表型具有重要的意义。(生物谷Bioon.com)
生物谷推荐原始出处:
Developmental Cell, 06 November 2008 doi:10.1016/j.devcel.2008.10.005
Dynamic Regulation by Polycomb Group Protein Complexes Controls Pattern Formation and the Cell Cycle in Drosophila
Katarzyna Oktaba1, 3, Luis Gutiérrez1, 3, Julien Gagneur2, Charles Girardot2, Aditya K. Sengupta1, Eileen E.M. Furlong2 and Jürg Müller1, ,
1 EMBL, Gene Expression Programme, Meyerhofstrasse 1, 69117 Heidelberg, Germany
2 EMBL, Developmental Biology Programme, Meyerhofstrasse 1, 69117 Heidelberg, Germany
3 These authors contributed equally to this work
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.