Abstract
Enhancers are cis-regulatory elements that enable precise spatiotemporal patterns of gene expression during development and are notable for being able to function at large distances from their target genes. Such regulatory elements often bypass intervening genes and typically comprise binding sites for multiple transcription factors that can also be transcribed by RNA polymerase II (Pol II) to produce noncoding enhancer RNAs (eRNAs). Genome-wide analyses have revealed chromatin signatures of enhancers, such as the enrichment for monomethylation of histone H3 lysine 4 (H3K4me1) and the acetylation or methylation of histone H3 lysine 27 (H3K27). Enhancer signatures have been used to describe the transitions of these regulatory elements from inactive to primed and from activated to decommissioned states during development. New mutations of enhancer sequences and of the protein factors regulating enhancer function in human disease continue to be identified, contributing to a growing class of 'enhanceropathies'.
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Acknowledgements
We thank D. Dorsett and H.-M. Herz for helpful discussions, M. Miller for preparation of figures, M. Morgan for the term 'enhanceropathy', and L. Shilatifard and L. Kennedy for editorial assistance. The work on enhancers in the Shilatifard laboratory is funded by US National Institutes of Health grants R01CA150265 and R01CA89455.
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Smith, E., Shilatifard, A. Enhancer biology and enhanceropathies. Nat Struct Mol Biol 21, 210–219 (2014). https://doi.org/10.1038/nsmb.2784
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DOI: https://doi.org/10.1038/nsmb.2784
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