Targeting Super-Enhancers for Disease Treatment and Diagnosis

Mol Cells. 2018 Jun;41(6):506-514. doi: 10.14348/molcells.2018.2297. Epub 2018 May 10.

Abstract

The transcriptional regulation of genes determines the fate of animal cell differentiation and subsequent organ development. With the recent progress in genome-wide technologies, the genomic landscapes of enhancers have been broadly explored in mammalian genomes, which led to the discovery of novel specific subsets of enhancers, termed super-enhancers. Super-enhancers are large clusters of enhancers covering the long region of regulatory DNA and are densely occupied by transcription factors, active histone marks, and co-activators. Accumulating evidence points to the critical role that super-enhancers play in cell type-specific development and differentiation, as well as in the development of various diseases. Here, I provide a comprehensive description of the optimal approach for identifying functional units of super-enhancers and their unique chromatin features in normal development and in diseases, including cancers. I also review the recent updated knowledge on novel approaches of targeting super-enhancers for the treatment of specific diseases, such as small-molecule inhibitors and potential gene therapy. This review will provide perspectives on using super-enhancers as biomarkers to develop novel disease diagnostic tools and establish new directions in clinical therapeutic strategies.

Keywords: cell identity; clinical therapeutics; disease diagnosis; diseases; super-enhancer.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Differentiation
  • Disease / genetics*
  • Enhancer Elements, Genetic / genetics*
  • Humans