Enhanced Identification of Transcriptional Enhancers Provides Mechanistic Insights into Diseases

Enhancers are distal cis-regulatory DNA elements that increase the expression of target genes. Various experimental and computational approaches including chromatin signature profiling have been developed to predict enhancers on a genome-wide scale, although each method has its advantages and disadvantages. Here we overview an emerging method to identify transcribed enhancers at exceedingly high nucleotide resolution based on enhancer RNA transcripts captured by Cap Analysis of Gene Expression (CAGE) technology. We further argue that disease-causative regulatory mutations at enhancers are increasingly recognized, emphasizing the importance of enhancer identification in functional and clinical genomics including, but not limited to, genome-wide association studies (GWASs) and cancer genomics studies.

TrendsVarious experimental and computational approaches have been developed to predict enhancers on a genome-wide scale, although each method has its advantages and disadvantages.Cap analysis of gene expression (CAGE) identifies transcribed enhancers at exceedingly high nucleotide resolution by detecting enhancer RNAs (eRNAs).Disease-associated SNPs and recurrent somatic cancer mutations are identified within enhancers. These variants might alter enhancer activities and contribute to pathogenesis, highlighting the importance of enhancer identification in various clinical settings.