美国国立卫生研究院(NIH)旗下的心肺血液研究所分子免疫学实验室,华盛顿大学生理系的科学家在组蛋白乙酰转移酶和脱乙酰基酶对基因活化的研究上取得了新的进展,成果文章Genome-wide Mapping of HATs and HDACs Reveals Distinct Functions in Active and Inactive Genes发表在Cell在线版上。
组蛋白乙酰转移酶(HAT)及脱乙酰基酶(HDAC)调节组蛋白和转录因子的乙酰化水平,从而在控制细胞生命活动中发挥着重要作用。
乙酰化是组蛋白激活开始转录的标记,可以说HATs是基因表达被激活的标记,而HDACs是基因表达失活的标记。
在本研究中,Zhao教授研究小组通过全基因组扫描的方式鉴定与乙酰化组蛋白相关的活性基因。研究结果表明,HATs和HDACs作用的靶位是活性基因的转录区域。HDACs在人类基因组上的作用是消除活性基因的乙酰化,重新激活基因表达系统。
而无表达活性的基因则发生MLL介导的组蛋白H3K4甲基化进入HAT/HDAC的乙酰化和脱乙酰化的循环周期,阻止Pol Ⅱ与基因结合,确保基因不被表达。沉默的基因没有H3K4甲基化信号则表明没有与HDACs结合。
这些数据表明,HAT与HDAC在活性基因与沉默基因中发挥不同的功效。(生物谷Bioon.com)
生物谷推荐原始出处:
Cell, 20 August 2009 doi:10.1016/j.cell.2009.06.049
Genome-wide Mapping of HATs and HDACs Reveals Distinct Functions in Active and Inactive Genes
Zhibin Wang1,3,Chongzhi Zang2,3,Kairong Cui1,3,Dustin E. Schones1,Artem Barski1,Weiqun Peng2andKeji Zhao1,,
1 Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
2 Department of Physics, The George Washington University, Washington D.C. 20052, USA
Histone acetyltransferases (HATs) and deacetylases (HDACs) function antagonistically to control histone acetylation. As acetylation is a histone mark for active transcription, HATs have been associated with active and HDACs with inactive genes. We describe here genome-wide mapping of HATs and HDACs binding on chromatin and find that both are found at active genes with acetylated histones. Our data provide evidence that HATs and HDACs are both targeted to transcribed regions of active genes by phosphorylated RNA Pol II. Furthermore, the majority of HDACs in the human genome function to reset chromatin by removing acetylation at active genes. Inactive genes that are primed by MLL-mediated histone H3K4 methylation are subject to a dynamic cycle of acetylation and deacetylation by transient HAT/HDAC binding, preventing Pol II from binding to these genes but poising them for future activation. Silent genes without any H3K4 methylation signal show no evidence of being bound by HDACs.