Prokhorov General Physics Institute of the Russian Academy of Sciences, 38 Vavilov St., 119991 Moscow, Russia.
Faculty of Biology, Lomonosov Moscow State University, Leninskiye Gory, MSU, 1-12, 119991 Moscow, Russia.
Cells. 2023 Apr 19;12(8):1191. doi: 10.3390/cells12081191.
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.
超级增强子（SEs）是人类基因组中的顺式调控元件，自该术语的发现和起源以来，一直受到广泛讨论。已经表明，超级增强子与细胞分化、细胞稳定性维持和肿瘤发生的关键基因的表达密切相关。我们的目标是系统地研究专门用于研究超级增强子结构和功能的研究，并在各种应用中（如药物开发和临床使用）定义该领域的进一步前景。我们综述了基础研究，这些研究提供了有关各种病理学及其与特定超级增强子关联的实验数据。对 SE 搜索和预测的主流方法的分析使我们能够积累现有数据，并为进一步提高 SE 可靠性水平和效率的算法改进提出方向。因此，在这里我们描述了最稳健的算法，如 ROSE、imPROSE 和 DEEPSEN，并建议将它们进一步用于各种研究和开发任务。基于主题和发表研究数量的最有前途的研究方向是与癌症相关的超级增强子和有前景的 SE 靶向治疗策略，本综述讨论了其中的大部分内容。
