Demystifying the secret mission of enhancers: linking distal regulatory elements to target genes.

Crit Rev Biochem Mol Biol 2015 8;50(6):550-73. Epub 2015 Oct 8.

a Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California , Los Angeles , CA , USA and.

Enhancers are short regulatory sequences bound by sequence-specific transcription factors and play a major role in the spatiotemporal specificity of gene expression patterns in development and disease. While it is now possible to identify enhancer regions genomewide in both cultured cells and primary tissues using epigenomic approaches, it has been more challenging to develop methods to understand the function of individual enhancers because enhancers are located far from the gene(s) that they regulate. However, it is essential to identify target genes of enhancers not only so that we can understand the role of enhancers in disease but also because this information will assist in the development of future therapeutic options. After reviewing models of enhancer function, we discuss recent methods for identifying target genes of enhancers. First, we describe chromatin structure-based approaches for directly mapping interactions between enhancers and promoters. Second, we describe the use of correlation-based approaches to link enhancer state with the activity of nearby promoters and/or gene expression. Third, we describe how to test the function of specific enhancers experimentally by perturbing enhancer-target relationships using high-throughput reporter assays and genome editing. Finally, we conclude by discussing as yet unanswered questions concerning how enhancers function, how target genes can be identified, and how to distinguish direct from indirect changes in gene expression mediated by individual enhancers.

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Source
http://dx.doi.org/10.3109/10409238.2015.1087961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4666684PMC
September 2016
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