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Nat Rev Mol Cell Biol. 2015 Mar;16(3):144-54. doi: 10.1038/nrm3949. Epub 2015 Feb 4.

The selection and function of cell type-specific enhancers.

Author information

1
Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, San Diego, California 92037, USA.
2
Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, San Diego, California 92093, USA.
3
1] Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, San Diego, California 92093, USA. [2] Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, San Diego, California 92093, USA.

Abstract

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.

PMID:
25650801
PMCID:
PMC4517609
DOI:
10.1038/nrm3949
[Indexed for MEDLINE]
Free PMC Article
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