Histone Modifications at Human Enhancers Reflect Global Cell-Type-Specific Gene Expression
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Kellis_Histone Modifications.pdf
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2.8 MB
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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.
Date Issued
March 2009
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
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.
MIT Department
Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
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Creative Commons Attribution-Noncommercial-Share Alike 3.0
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DOI of Published Version
https://doi.org/10.1038/nature07829
