Journal
NATURE REVIEWS MOLECULAR CELL BIOLOGY
Volume 16, Issue 3, Pages 144-154Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nrm3949
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Funding
- US National Institutes of Health (NIH) [DK091183, CA17390, DK063491]
- San Diego Center for Systems Biology
- American Heart Association [12POST11760017]
- NIH Pathway to Independence Award [1K99HL12348]
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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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