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Review
, 41 (6), 506-514

Targeting Super-Enhancers for Disease Treatment and Diagnosis

Affiliations
Review

Targeting Super-Enhancers for Disease Treatment and Diagnosis

Ha Youn Shin. Mol Cells.

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.

Figures

Fig. 1
Fig. 1. Schematic diagrams of the chromatin structure of super-enhancers and an approach to identify super-enhancers
(A) Comparison of super-enhancers and typical enhancers. In contrast to typical enhancers, super-enhancers comprise large clusters of enhancers that are densely occupied with H3K27ac, MED1, and lineage-specific or master transcription factors. (B) Simple flow chart of super-enhancer isolation steps. After non-promoter regions are extracted, super-enhancers are isolated against single factors, including H3K27ac, MED1, and lineage-specific- and master transcription factors using the ROSE algorithm. Only the overlapped super-enhancers that link to cell-type-specific genes are isolated as high-confidence super-enhancers.
Fig. 2
Fig. 2. Establishment of oncogenic super-enhancers in cancers
(A) Mutations found in super-enhancers. (B) Newly acquired oncogenic super-enhancers by small indels, DNA translocation, focal amplification, and transcription factor overexpression.

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