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The selection and function of cell type-specific enhancers
Open accessAbstract
The human body contains several hundred cell types, all of which share the same genome. In metazoans, much of the regulatory code that drives cell type-specific gene expression is located in distal elements called enhancers. Although mammalian genomes contain millions of potential enhancers, only a small subset of them is active in a given cell type. Cell type-specific enhancer selection involves the binding of lineage-determining transcription factors that prime enhancers. Signal-dependent transcription factors bind to primed enhancers, which enables these broadly expressed factors to regulate gene expression in a cell type-specific manner. The expression of genes that specify cell type identity and function is associated with densely spaced clusters of active enhancers known as super-enhancers. The functions of enhancers and super-enhancers are influenced by, and affect, higher-order genomic organization.
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“Based on ChIP-seq and Assay for Transposase Accessible Chromatin using sequencing (ATAC-seq), H3K27ac was enriched in accessible regions, consistent with the known association of H3K27ac with active promoters and enhancers (Heinz et al., 2015; Klemm et al., 2019).”
From Loss of epigenetic information as a cause of mammalian aging (2023) · cites this paper as Heinz et al., 2015
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“Unique enhancer repertoires underly particular patterns of gene expression and enable cell type-specific responses (7).”
From Brain cell type–specific enhancer–promoter interactome maps and disease - risk association (2019) · cites this paper as [7]
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“The performance improvement was largest for CAGE, possibly because tissue-specific gene expression strongly depends on distal elements11.”
From Effective gene expression prediction from sequence by integrating long-range interactions (2021) · cites this paper as [11]
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“Regardless of any such mechanistic heterogeneity, a common property is that the activity of individual enhancers is generally cell-type-specific or even condition-specific99, and this specificity is a function of the expression levels of the TFs that are able to bind to it89.”
From Towards a comprehensive catalogue of validated and target-linked human enhancers (2020) · cites this paper as [89]
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“Enhancers are ‘punctate’ relative to broader chromatin domains (e.g. chromosomes, topologically associating domains [G] (TADs) and sub-compartments of TADs87), but their in vivo functionality is dependent on both the chromatin context in which they reside88 and on the trans milieu (e.g. cell-type-specific TFs)89.”
From Towards a comprehensive catalogue of validated and target-linked human enhancers (2020) · cites this paper as [89]
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Metadata
- Authors
- Heinz, S., Romanoski, C. E., Benner, C., & Glass, C. K.
- Affiliations
- Salk Institute for Biological Studies (US)
- University of California San Diego (US)
- Corresponding author
- Glass, Christopher K.
- Venue
- Nature Reviews Molecular Cell Biology
- Published
- 2015-02-04
- Volume
- 16
- Issue
- 3
- Pages
- 144-154
- ISSN
- 1471-0072 (ISSN-L)
- 1471-0080
- PMC
- PMC4517609
- OpenAlex
- W2063815548
- Cited by
- 1,010
- References
- 131
- Citations by year
- 2026: 75 · 2025: 77 · 2024: 86 · 2023: 85 · 2022: 97 · 2021: 87 · 2020: 109 · 2019: 103 · 2018: 100 · 2017: 94 · 2016: 67 · 2015: 30
- FWCI
- 9.40
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Molecular Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (1K99HL12348)
- National Cancer Institute (R01CA173903, CA17390)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK063491, DK091183, P30DK063491, R01DK091183)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- enhancers, super-enhancers, cell type-specific gene expression, transcription factors, chromatin organization, 3D genome organization, distal regulatory elements
- MeSH terms
- Animals, Cell Differentiation, Chromatin, Enhancer Elements, Genetic, Eukaryotic Cells, Histones, Humans, Organ Specificity, Transcription Factors, Transcription, Genetic, Genome, Gene Expression Regulation, Developmental, Cell Lineage
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