Whitehead生物醫(yī)學(xué)研究所聯(lián)合麻省理工生物系的科學(xué)家對(duì)干細(xì)胞的定向發(fā)育DNA調(diào)控機(jī)制又有新發(fā)現(xiàn),，研究者在ES細(xì)胞（胚胎干細(xì)胞）定向各譜系發(fā)育的過(guò)程中發(fā)現(xiàn),，H2AZ在多個(gè)靶位基因中發(fā)現(xiàn)有豐富的表達(dá)量。這一成果公布在11月6日Cell online版上,。
生命起源于胚胎干細(xì)胞,，生物的多樣性來(lái)自于干細(xì)胞的多能性,。胚胎干細(xì)胞的發(fā)育是一個(gè)復(fù)雜的生理過(guò)程,，在胚胎干細(xì)胞的分化發(fā)育過(guò)程中受多個(gè)基因的調(diào)控，這一過(guò)程也一直是科學(xué)家們亟待了解的神秘過(guò)程,。尤其是對(duì)胚胎干細(xì)胞的了解有助于了解人類(lèi)疾病的發(fā)生發(fā)展機(jī)制,。因此，干細(xì)胞發(fā)育與基因調(diào)節(jié)的關(guān)系就成為研究者不懈努力的方向,。
研究發(fā)現(xiàn),，變異的組蛋白H2AZ在染色質(zhì)功能的發(fā)育過(guò)程中是一個(gè)關(guān)鍵的調(diào)控因子，對(duì)基因表達(dá)等功能其重要的作用,，但是人們卻一直沒(méi)有揭開(kāi)H2AZ組蛋白的神秘面紗,，究竟它是如何發(fā)揮作用，人們一無(wú)所知,。
在本文章中,，麻省理工和哈佛白頭研究所的科學(xué)家將從基因組學(xué)的水平分析H2AZ，新的研究結(jié)果表明H2AZ的作用模式與PcG（Polycomb group）蛋白Suz12驚人的相似,，它們是某些重要的基因的啟動(dòng)子蛋白,。
研究小組用RNAi技術(shù)來(lái)研究?jī)蓚€(gè)蛋白的功能，結(jié)果發(fā)現(xiàn)H2AZ與PcG蛋白是獨(dú)立執(zhí)行功能的蛋白,，對(duì)靶基因的表達(dá)具有重要的調(diào)控作用,。更值得關(guān)注的是，H2AZ蛋白是調(diào)控胚胎干細(xì)胞分化的關(guān)鍵因子,。H2AZ蛋白在某一特別的細(xì)胞亞類(lèi)中的表達(dá)量十分高,，這表明H2AZ蛋的分配量是影響細(xì)胞命運(yùn)關(guān)鍵蛋白,。
因此說(shuō)，H2AZ與PcG蛋白在干細(xì)胞的分化過(guò)程中起關(guān)鍵的作用,，它們通過(guò)調(diào)節(jié)基因表達(dá)來(lái)促進(jìn)胚胎干細(xì)胞分化,。（生物谷Bioon.com）
生物谷推薦原始出處：
Cell, 06 November 2008 doi:10.1016/j.cell.2008.09.056
H2AZ Is Enriched at Polycomb Complex Target Genes in ES Cells and Is Necessary for Lineage Commitment
Menno P. Creyghton1,3,Styliani Markoulaki1,3,Stuart S. Levine1,Jacob Hanna1,Michael A. Lodato1,2,Ky Sha2,Richard A. Young1,2,Rudolf Jaenisch1,2andLaurie A. Boyer2,,
1 Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
2 Massachusetts Institute of Technology, Department of Biology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
3 These authors contributed equally to this work
SUMMARY
Elucidating how chromatin influences gene expression patterns and ultimately cell fate is fundamental to understanding development and disease. The histone variant H2AZ has emerged as a key regulator of chromatin function and plays an essential but unknown role during mammalian development. Here, genome-wide analysis reveals that H2AZ occupies the promoters of developmentally important genes in a manner that is remarkably similar to that of the Polycomb group (PcG) protein Suz12. By using RNAi, we demonstrate a role for H2AZ in regulating target gene expression, find that H2AZ and PcG protein occupancy is interdependent at promoters, and further show that H2AZ is necessary for ES cell differentiation. Notably, H2AZ occupies a different subset of genes in lineage-committed cells, suggesting that its dynamic redistribution is necessary for cell fate transitions. Thus, H2AZ, together with PcG proteins, may establish specialized chromatin states in ES cells necessary for the proper execution of developmental gene expression programs.
