质谱技术鉴定细胞中组蛋白翻译后修饰的研究进展  

Development of Identification for Post-Translational Modifications in Histones by Mass Spectrometry Based Proteomics

作　　者：陈英[1] 张锴[1] 何锡文[1] 张玉奎[1,2] 

机构地区：[1]南开大学化学学院,天津300071 [2]中国科学院大连化学物理研究所,大连116023

出　　处：《化学进展》2010年第4期713-719,共7页Progress in Chemistry

基　　金：国家自然科学基金项目(No.90919008;20975053和U0932001);国家重点基础研究发展计划(973)项目(No.2007CB914100);NN-CAS-2008-8项目资助

摘　　要：组蛋白是真核细胞中构成染色质内核小体的主要元件,其翻译后修饰蕴藏着组蛋白密码,是表观遗传学的重要内容,影响染色质的结构和功能,进而调控基因表达。组蛋白翻译后修饰形式的鉴定是揭示组蛋白密码的关键,目前质谱技术已经成为分析组蛋白及其翻译后修饰的重要工具。本文综述了组蛋白翻译后修饰鉴定方法的新进展,介绍了基于质谱技术"bottom-up"和"top-down"的组蛋白分析策略,及CID、ECD和ETD等鉴定组蛋白修饰位点的质谱碎片裂解技术,并结合当前研究进展,评述了质谱技术在组蛋白翻译后修饰谱的鉴定、组蛋白各种变体的测定,以及在生理过程中组蛋白修饰丰度动态变化的定量分析等方面应用的新进展。In eukaryotic cells,chromosomal DNA is packaged into a compact structure,chromatin,with the help of four core histones.The fundamental repeating unit of chromatin is the nucleosome,which contains an octamer of core histones,around 147 base pairs of DNA are wrapped.Post-translational modifications（PTMs） in histones are generally considered to be a major group of epigenetic marks.Accordingly,because PTMs alter the properties of histones,hence affect chromatin structure and function and regulate the gene expression.Therefore identification of histone PTMs is the key to discover histone codes.At present,mass spectrometry has become a powerful analysis tool.In this paper we introduced the novel development of the strategies based on mass spectrometry（＂bottom-up＂and＂top-down＂） in mapping histone PTMs,fragment dissociation technologies such as CID、ECD and ETD.We also reported the application of mass spectrometry in addressing histone PTMs sites、 identifying histone variants and quantifying differential expression of these PTMs in cells.

关 键 词：组蛋白 翻译后修饰 质谱 高效液相色谱 

分 类 号：O629.7[理学—有机化学] O657.6[理学—化学]