最近的Nature在线版刊登了一篇题为：Histone modifications at human enhancers reflect global cell-type-specific gene expression的文章，主要解析了组蛋白修饰对细胞分化命运的控制机制。
人类生命体由多种不同的组织、器官组成，组成不同组织器官的基础物质是细胞，在人体内有多种不同类型不同功能的专门细胞。尽管研究者一直都知道细胞的谱系分化是由基因调控的，不同类型的细胞具有不同的启动子，增强子，以及其他基因表达调控的顺式调控子。但是具体哪种细胞由哪种启动子等调控序列来控制科学家们暂时没有找到答案。
研究小组希望探索这一机制，先前他们用一种基于DNA-蛋白交联基础上的染色质免疫沉淀（ChIP-chip）技术定位了人类基因组上的启动子，增强子和绝缘子（insulator）。在本次研究中，研究者用相同的技术定位不同类型细胞的启动子，增强子等，对这些调控子在细胞分化命运中所起的作用进行详细分析。
最终，研究小组在人类基因组上鉴定了55,000种潜在的转录增强子，这些研究结果大大的扩增了人类对增强子的了解，也丰富了增强子的内容，这些增强子等顺式调控因子对细胞的分化命运具有重要的意义。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature , doi:10.1038/nature07829; Received 17 October 2008; Accepted 26 January 2009; Published online 18 March 2009
Histone modifications at human enhancers reflect global cell-type-specific gene expression
Nathaniel D. Heintzman1,2,12, Gary C. Hon1,3,12, R. David Hawkins1,12, Pouya Kheradpour5, Alexander Stark5,6, Lindsey F. Harp1, Zhen Ye1, Leonard K. Lee1, Rhona K. Stuart1, Christina W. Ching1, Keith A. Ching1, Jessica E. Antosiewicz-Bourget7, Hui Liu8, Xinmin Zhang8, Roland D. Green8, Victor V. Lobanenkov9, Ron Stewart7, James A. Thomson7,10, Gregory E. Crawford11, Manolis Kellis5,6 & Bing Ren1,4
1 Ludwig Institute for Cancer Research,
2 Biomedical Sciences Graduate Program,
3 Bioinformatics Program, and,
4 Department of Cellular and Molecular Medicine, UCSD School of Medicine, 9500 Gilman Drive, La Jolla, California 92093-0653, USA
5 MIT Computer Science and Artificial Intelligence Laboratory, 32 Vassar Street, Cambridge, Massachusetts 02139, USA
6 Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
7 Morgridge Institute for Research, Madison, Wisconsin 53707-7365, USA
8 Roche NimbleGen, Inc., 500 South Rosa Road, Madison, Wisconsin 53719, USA
9 National Institutes of Allergy and Infectious Disease, 5640 Fishers Lane, Rockville, Maryland 20852, USA
10 University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53706, USA
11 Institute for Genome Sciences and Policy, and Department of Pediatrics, Duke University, 101 Science Drive, Durham, North Carolina 27708, USA
12 These authors contributed equally to this work.
13 Correspondence to: Bing Ren1,4 Correspondence and requests for materials should be addressed to B.R.
The human body is composed of diverse cell types with distinct functions. Although it is known that lineage specification depends on cell-specific gene expression, which in turn is driven by promoters, enhancers, insulators and other cis-regulatory DNA sequences for each gene1, 2, 3, the relative roles of these regulatory elements in this process are not clear. We have previously developed a chromatin-immunoprecipitation-based microarray method (ChIP-chip) to locate promoters, enhancers and insulators in the human genome4, 5, 6. Here we use the same approach to identify these elements in multiple cell types and investigate their roles in cell-type-specific gene expression. We observed that the chromatin state at promoters and CTCF-binding at insulators is largely invariant across diverse cell types. In contrast, enhancers are marked with highly cell-type-specific histone modification patterns, strongly correlate to cell-type-specific gene expression programs on a global scale, and are functionally active in a cell-type-specific manner. Our results define over 55,000 potential transcriptional enhancers in the human genome, significantly expanding the current catalogue of human enhancers and highlighting the role of these elements in cell-type-specific gene expression.
