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Histone Modifications at Human Enhancers Reflect Global Cell-Type-Specific Gene Expression

Author(s)
Heintzman, Nathaniel D.; Hon, Gary C.; Hawkins, R. David; Kheradpour, Pouya; Stark, Alexander; Harp, Lindsey F.; Ye, Zhen; Lee, Leonard K.; Stuart, Rhona K.; Ching, Christina W.; Ching, Keith A.; Antosiewicz-Bourget, Jessica E.; Liu, Hui; Zhang, Xinmin; Green, Roland D.; Lobanenkov, Victor V.; Stewart, Ron; Thomson, James A.; Crawford, Gregory E.; Kellis, Manolis; Ren, Bing; ... Show more Show less
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Abstract
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.
Date issued
2009-03
URI
http://hdl.handle.net/1721.1/72981
Department
Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory; Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
Journal
Nature
Publisher
Nature Publishing Group
Citation
Heintzman, Nathaniel D. et al. “Histone Modifications at Human Enhancers Reflect Global Cell-type-specific Gene Expression.” Nature 459.7243 (2009): 108–112.
Version: Author's final manuscript
ISSN
0028-0836
1476-4687

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