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Histone modifications at human enhancers reflect global cell-type-specific gene expression
Open accessAbstract
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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“ChIPseq using antibodies to H3K4Me3, a mark associated with active promoter sites (Ernst et al., 2011), and to H3K27Ac, a mark associated with enhancer elements (Heintzman et al., 2009), demonstrated mapped read peaks corresponding to at least four major transcriptional start sites within the SYNE1 locus (P1–P4), one of which (P3) lies immediately upstream of the p.L3206M mutation (Figure 3E).”
From Using Whole-Exome Sequencing to Identify Inherited Causes of Autism (2013) · cites this paper as Heintzman et al., 2009
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Metadata
- 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
- Venue
- Nature
- Published
- 2009-03-18
- Volume
- 459
- Issue
- 7243
- Pages
- 108-112
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- 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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