6月22日,,Cell雜志報(bào)道了染色質(zhì)重構(gòu)調(diào)節(jié)子在核小體中特異性和方向性的最新研究成果。
眾多染色質(zhì)重構(gòu)調(diào)節(jié)子是如何相互合作,,在基因的開始和結(jié)束位點(diǎn)處組織核小體的還不清楚,。研究者發(fā)現(xiàn)在釀酒酵母細(xì)胞全基因組范圍內(nèi),SWI/ SNF,,RSC,,ISW1a,ISW1b,ISW2,,INO80等染色質(zhì)重構(gòu)調(diào)節(jié)子復(fù)合體與單個(gè)核小體相結(jié)合,,并通過缺失分析證實(shí),這些復(fù)合體通過輔助核小體定位行使其功能,。
研究者采用超高分辨率ChIP-exo(一種基于染色質(zhì)免疫沉淀的基因組作圖方法,,用于確定目標(biāo)蛋白質(zhì)結(jié)合到基因組的位置)研究Isw2基因,以在基因組范圍內(nèi)確定其組織模式和在核小體內(nèi)的定位方向,。
研究發(fā)現(xiàn),,染色質(zhì)重構(gòu)調(diào)節(jié)子在基因的起始和結(jié)束位置與特定核小體位點(diǎn)相互作用,并在移動(dòng)中的核小體內(nèi),,基因的5'和3'末端產(chǎn)生朝向或背向無核小體基因組區(qū)域的定向性,。根據(jù)其生化和晶體結(jié)構(gòu)信息建立的模型,研究者將isw2的連接子結(jié)合區(qū)域定位于基因啟動(dòng)子內(nèi)部,,與Reb1因子結(jié)合的位點(diǎn)緊靠,。(生物谷bioon.com)
doi:10.1016/j.cell.2011.10.017
PMC:
PMID:
Genome-wide Nucleosome Specificity and Directionality of Chromatin Remodelers
Kuangyu Yen, Vinesh Vinayachandran, Kiran Batta, R. Thomas Koerber, B. Franklin Pugh
How chromatin remodelers cooperate to organize nucleosomes around the start and end of genes is not known. We determined the genome-wide binding of remodeler complexes SWI/SNF, RSC, ISW1a, ISW1b, ISW2, and INO80 to individual nucleosomes in Saccharomyces, and determined their functional contributions to nucleosome positioning through deletion analysis. We applied ultra-high-resolution ChIP-exo mapping to Isw2 to determine its subnucleosomal orientation and organization on a genomic scale. Remodelers interacted with selected nucleosome positions relative to the start and end of genes and produced net directionality in moving nucleosomes either away or toward nucleosome-free regions at the 5 and 3 ends of genes. Isw2 possessed a subnucleosomal organization in accord with biochemical and crystallographic-based models that place its linker binding region within promoters and abutted against Reb1-bound locations. Together, these findings reveal a coordinated position-specific approach taken by remodelers to organize genic nucleosomes into arrays.