歐洲分子生物學(xué)實(shí)驗(yàn)所位于德國(guó)漢堡的表觀基因研究項(xiàng)目組和發(fā)育生物學(xué)項(xiàng)目組的科學(xué)家以果蠅為研究模型,,揭示復(fù)雜的Polycomb Group Protein Complexes對(duì)細(xì)胞形成和細(xì)胞分裂模式的動(dòng)力控制機(jī)制。相關(guān)文章發(fā)表在11月6日Cell子刊Development Cell在線版上,。
Polycomb Group(PcG )蛋白形成保守的調(diào)控復(fù)合物,,對(duì)染色質(zhì)的表達(dá)轉(zhuǎn)錄具有修飾作用。研究小組從整個(gè)基因組范圍以及相關(guān)的結(jié)合蛋白PhoRC研究果蠅的PcG蛋白復(fù)合物,,包括其中的DNA結(jié)合因子Pho/dYY1和dSfmbt,。在果蠅胚胎與幼蟲發(fā)育階段,PhoRC構(gòu)成短調(diào)節(jié)基因表達(dá)的Polycomb效應(yīng)元素(short Polycomb response elements,PREs),。
PREs與PcG復(fù)合物PRC1和PRC2共同出現(xiàn),。對(duì)PcG突變體研究發(fā)現(xiàn),PcG系統(tǒng)表達(dá)基因在幼蟲發(fā)育的前端,、背腹以及遠(yuǎn)端模式都是必須的,,同時(shí)可抑制細(xì)胞分裂調(diào)節(jié)基因的活性。大量的基因群以動(dòng)態(tài)的調(diào)節(jié)模式工作,,研究小組的研究結(jié)果表明,,PcG系統(tǒng)限制部分細(xì)胞的信號(hào)介導(dǎo)的靶基因活性。對(duì)細(xì)胞分裂調(diào)節(jié)研究發(fā)現(xiàn),PcG系統(tǒng)在某些基因表達(dá)的模式上是以動(dòng)態(tài)的形式進(jìn)行的,,這為研究腫瘤的PcG突變表型具有重要的意義,。(生物谷Bioon.com)
生物谷推薦原始出處:
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.