Genome-Wide Maps of Transcription Regulatory Elements and Transcription Enhancers in Development and Disease

Gene expression is regulated by numerous elements including enhancers, insulators, transcription factors, and architectural proteins. Regions of DNA distal to the transcriptional start site, called enhancers, play a central role in the temporal and tissue-specific regulation of gene expression through RNA polymerase II. The identification of enhancers and other cis regulatory elements has largely been possible due to advances in next generation sequencing technologies. Enhancers regulate gene expression through chromatin loops mediated by architectural proteins such as YY1, CTCF, the cohesin complex, and LDB1. Additionally, enhancers can be transcribed to produce noncoding RNAs termed enhancer RNAs that likely participate in transcriptional regulation. The central role of enhancers in regulating gene expression implicates them in both normal physiology but also many disease states. The importance of enhancers is evident by the suggested role of SNPs, duplications, and other alterations of enhancer function in many diseases, ranging from cancer to atherosclerosis to chronic kidney disease. Although much progress has been made in recent years, the field of enhancer biology and our knowledge of the cis regulome remains a work in progress. This review will highlight recent seminal studies which demonstrate the role of enhancers in normal physiology and disease pathogenesis. © 2019 American Physiological Society. Compr Physiol 9:439-455, 2019.