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

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

Ekaterina V Kravchuk  1   2 , German A Ashniev  1   2   3 , Marina G Gladkova  3 , Alexey V Orlov  1 , Anastasiia V Vasileva  1 , Anna V Boldyreva  1 , Alexandr G Burenin  1 , Artemiy M Skirda  1 , Petr I Nikitin  1 , Natalia N Orlova  1
Affiliations
Review

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

Ekaterina V Kravchuk et al. Cells. .

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.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; in the decision to publish the results.

Figures

Figure 1
Figure 1
Schematic representation of the SE concept compared to the TE. (A). LLPS model (blue circle) inside a TAD with two differentially active SEs, which are surrounded by the elements of transcription activation complex and RNAP II. (B). The TE structure, being less lengthy compared to its SE analogues and comprising one distinct TE region, shows moderate levels of H3K27ac signaling.
Figure 2
Figure 2
Currently implemented models for predicting super-enhancers. (A) ROSE; (B) imPROSE; (C) DEEPSEEN; (D) DeepSE.
Figure 3
Figure 3
SE-regulated transcription inhibitors that can be used for cancer therapy.
See this image and copyright information in PMC

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