Cited by 2,533Genomics and Chromatin DynamicsEpigenetics and DNA MethylationChromatin Remodeling and Cancer

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Histone modifications at human enhancers reflect global cell-type-specific gene expression

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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·2009·Nature

DOI 10.1038/nature07829PMC PMC2910248

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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 gene, 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 genome. 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.

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Authors: Heintzman, N. D., Hon, G. C., Hawkins, R. D., Kheradpour, P., Stark, A., Harp, L. F., Ye, Z., Lee, L. K., Stuart, R. K., Ching, C. W., Ching, K. A., Antosiewicz-Bourget, J. E., Liu, H., Zhang, X., Green, R. D., Lobanenkov, V. V., Stewart, R., Thomson, J. A., Crawford, G. E., Kellis, M., & Ren, B.
Affiliations: Ludwig Cancer Research (BE)
MIT Computer Science and Artificial Intelligence Laboratory (US)
Broad Institute (US)
National Institute of Allergy and Infectious Diseases (US)
Morgridge Institute for Research (US)
University of Wisconsin–Madison (US)
Duke University (US)
Corresponding author: Ren, Bing
ORCID: Hon, Gary C.
Hawkins, R. David
Stark, Alexander
Ye, Zhen
Stuart, Rhona K.
Ching, Keith A.
Zhang, Xinmin
Lobanenkov, Victor V.
Stewart, Ron
Thomson, James A.
Crawford, Gregory E.
Kellis, Manolis
Ren, Bing
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2009-03-18
Volume: 459
Issue: 7243
Pages: 108-112
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature07829
PMC: PMC2910248
OpenAlex: W2123564569
Cited by: 2,533
References: 27
Citations by year: 2026: 56 · 2025: 101 · 2024: 115 · 2023: 122 · 2022: 101 · 2021: 126 · 2020: 171 · 2019: 150 · 2018: 163 · 2017: 154 · 2016: 164 · 2015: 183 · 2014: 193 · 2013: 204 · 2012: 188
FWCI: 71.06
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
RePEc: Research Papers in Economics (submittedVersion)
DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-sa)
PubMed Central
Funders: National Institutes of Health
National Human Genome Research Institute (U01HG003151, R01HG004037)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Keywords: histone modifications, enhancers, cell type-specific gene expression, promoter, insulators, CTCF binding, chromatin state, cis-regulatory elements, human cell lines, ChIP-chip
MeSH terms: Binding Sites, Cell Line, Cell Physiological Phenomena, Chromatin, Gene Expression Regulation, HeLa Cells, Histones, Humans, Promoter Regions, Genetic, Transcription Factors, Genome, Human, K562 Cells

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