最近的Nature在線版刊登了一篇題為：Histone modifications at human enhancers reflect global cell-type-specific gene expression的文章，主要解析了組蛋白修飾對(duì)細(xì)胞分化命運(yùn)的控制機(jī)制。
人類(lèi)生命體由多種不同的組織,、器官組成,，組成不同組織器官的基礎(chǔ)物質(zhì)是細(xì)胞，在人體內(nèi)有多種不同類(lèi)型不同功能的專(zhuān)門(mén)細(xì)胞,。盡管研究者一直都知道細(xì)胞的譜系分化是由基因調(diào)控的，不同類(lèi)型的細(xì)胞具有不同的啟動(dòng)子，增強(qiáng)子,，以及其他基因表達(dá)調(diào)控的順式調(diào)控子。但是具體哪種細(xì)胞由哪種啟動(dòng)子等調(diào)控序列來(lái)控制科學(xué)家們暫時(shí)沒(méi)有找到答案,。
研究小組希望探索這一機(jī)制,，先前他們用一種基于DNA-蛋白交聯(lián)基礎(chǔ)上的染色質(zhì)免疫沉淀（ChIP-chip）技術(shù)定位了人類(lèi)基因組上的啟動(dòng)子，增強(qiáng)子和絕緣子（insulator）,。在本次研究中,，研究者用相同的技術(shù)定位不同類(lèi)型細(xì)胞的啟動(dòng)子,，增強(qiáng)子等，對(duì)這些調(diào)控子在細(xì)胞分化命運(yùn)中所起的作用進(jìn)行詳細(xì)分析,。
最終,，研究小組在人類(lèi)基因組上鑒定了55,000種潛在的轉(zhuǎn)錄增強(qiáng)子，這些研究結(jié)果大大的擴(kuò)增了人類(lèi)對(duì)增強(qiáng)子的了解,，也豐富了增強(qiáng)子的內(nèi)容,，這些增強(qiáng)子等順式調(diào)控因子對(duì)細(xì)胞的分化命運(yùn)具有重要的意義。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
