Experimental Validation and Prediction of Super-Enhancers: Advances and Challenges

Cells. 2023 Apr 19;12(8):1191. doi: 10.3390/cells12081191.

Abstract

Super-enhancers (SEs) are cis-regulatory elements of the human genome that have been widely discussed since the discovery and origin of the term. Super-enhancers have been shown to be strongly associated with the expression of genes crucial for cell differentiation, cell stability maintenance, and tumorigenesis. Our goal was to systematize research studies dedicated to the investigation of structure and functions of super-enhancers as well as to define further perspectives of the field in various applications, such as drug development and clinical use. We overviewed the fundamental studies which provided experimental data on various pathologies and their associations with particular super-enhancers. The analysis of mainstream approaches for SE search and prediction allowed us to accumulate existing data and propose directions for further algorithmic improvements of SEs' reliability levels and efficiency. Thus, here we provide the description of the most robust algorithms such as ROSE, imPROSE, and DEEPSEN and suggest their further use for various research and development tasks. The most promising research direction, which is based on topic and number of published studies, are cancer-associated super-enhancers and prospective SE-targeted therapy strategies, most of which are discussed in this review.

Keywords: chromatin looping; drugs targeting chromatin interactions; experimental validation; regulation; super-enhancer; therapy.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinogenesis / genetics
  • Enhancer Elements, Genetic* / genetics
  • Humans
  • Neoplasms* / genetics
  • Prospective Studies
  • Reproducibility of Results

Grants and funding

This research was funded by the Russian Science Foundation, grant number 22-74-10053, https://rscf.ru/en/project/22-74-10053/, accessed on 6 March 2023 (research on the identification of super-enhancers as therapeutic targets and diagnostic markers) and 18-74-10098 (research devoted to the analysis of biomolecular interactions).