Whitehead生物医学研究所联合麻省理工生物系的科学家对干细胞的定向发育DNA调控机制又有新发现，研究者在ES细胞（胚胎干细胞）定向各谱系发育的过程中发现，H2AZ在多个靶位基因中发现有丰富的表达量。这一成果公布在11月6日Cell online版上。
生命起源于胚胎干细胞，生物的多样性来自于干细胞的多能性。胚胎干细胞的发育是一个复杂的生理过程，在胚胎干细胞的分化发育过程中受多个基因的调控，这一过程也一直是科学家们亟待了解的神秘过程。尤其是对胚胎干细胞的了解有助于了解人类疾病的发生发展机制。因此，干细胞发育与基因调节的关系就成为研究者不懈努力的方向。
研究发现，变异的组蛋白H2AZ在染色质功能的发育过程中是一个关键的调控因子，对基因表达等功能其重要的作用，但是人们却一直没有揭开H2AZ组蛋白的神秘面纱，究竟它是如何发挥作用，人们一无所知。
在本文章中，麻省理工和哈佛白头研究所的科学家将从基因组学的水平分析H2AZ，新的研究结果表明H2AZ的作用模式与PcG（Polycomb group）蛋白Suz12惊人的相似，它们是某些重要的基因的启动子蛋白。
研究小组用RNAi技术来研究两个蛋白的功能，结果发现H2AZ与PcG蛋白是独立执行功能的蛋白，对靶基因的表达具有重要的调控作用。更值得关注的是，H2AZ蛋白是调控胚胎干细胞分化的关键因子。H2AZ蛋白在某一特别的细胞亚类中的表达量十分高，这表明H2AZ蛋的分配量是影响细胞命运关键蛋白。
因此说，H2AZ与PcG蛋白在干细胞的分化过程中起关键的作用，它们通过调节基因表达来促进胚胎干细胞分化。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
