Abstract
Gene enhancer elements are noncoding segments of DNA that play a central role in regulating transcriptional programs that control development, cell identity, and evolutionary processes. Recent studies have shown that noncoding single nucleotide polymorphisms (SNPs) that have been associated with risk for numerous common diseases through genome-wide association studies frequently lie in cell-type-specific enhancer elements. These enhancer variants probably influence transcriptional output, thereby offering a mechanistic basis to explain their association with risk for many common diseases. This review focuses on the identification and interpretation of disease-susceptibility variants that influence enhancer function. We discuss strategies for prioritizing the study of functional enhancer SNPs over those likely to be benign, review experimental and computational approaches to identifying the gene targets of enhancer variants, and highlight efforts to quantify the impact of enhancer variants on target transcript levels and cellular phenotypes. These studies are beginning to provide insights into the mechanistic basis of many common diseases, as well as into how we might translate this knowledge for improved disease diagnosis, prevention and treatments. Finally, we highlight five major challenges often associated with interpreting enhancer variants, and discuss recent technical advances that may help to surmount these challenges.
Highlights
Transcriptional enhancer elements are noncoding stretches of DNA that have a central role in controlling gene expression programs in cells
More than 1,900 genome-wide association studies (GWASs) have been published, identifying loci associated with susceptibility to over 1,000 unique traits and common diseases [4]
Several groups have associated GWAS risk variants, mostly Single nucleotide polymorphism (SNP), with newly annotated cell-type-specific gene enhancer elements identified through epigenomic profiling studies
Summary
Transcriptional enhancer elements are noncoding stretches of DNA that have a central role in controlling gene expression programs in cells. Several groups have associated GWAS risk variants, mostly SNPs, with newly annotated cell-type-specific gene enhancer elements identified through epigenomic profiling studies These enhancer variants probably play an important part in common disease susceptibility by influencing transcriptional output. Further assessment of the effects of enhancer risk variants has shown that they can alter transcription-factor-binding sites (TFBSs) and impact the affinity of transcription factors for chromatin, and/or induce allele-specific effects on target gene expression [6,27,28,29,30,31,32,33,34,35,36,37,38,39,40] These studies illustrate the utility of epigenomic profiling for identifying risk variants that lie in putative enhancer elements and for identifying disease-relevant cell types in which the enhancer variants could exert their regulatory effects. Knowledge of gene targets may reveal pathways that are commonly altered among affected individuals, which could guide treatment strategies and rational drug design
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
