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

被引:7
作者
Kravchuk, Ekaterina V. [1 ,2 ]
Ashniev, German A. [1 ,2 ,3 ]
Gladkova, Marina G. [3 ]
Orlov, Alexey V. [1 ]
Vasileva, Anastasiia V. [1 ]
Boldyreva, Anna V. [1 ]
Burenin, Alexandr G. [1 ]
Skirda, Artemiy M. [1 ]
Nikitin, Petr I. [1 ]
Orlova, Natalia N. [1 ]
机构
[1] Russian Acad Sci, Prokhorov Gen Phys Inst, 38 Vavilov St, Moscow 119991, Russia
[2] Lomonosov Moscow State Univ, Fac Biol, Eninskiye Gory,MSU 1-121-12, Moscow 119991, Russia
[3] Lomonosov Moscow State Univ, Fac Bioengn & Bioinformat, GSP-1,Leninskiye Gory,MSU 1-73, Moscow 119234, Russia
基金
俄罗斯科学基金会;
关键词
super-enhancer; chromatin looping; therapy; regulation; experimental validation; drugs targeting chromatin interactions; TRANSCRIPTION FACTOR COOPERATIVITY; CORE REGULATORY CIRCUITRY; BROMODOMAIN PROTEIN BRD4; C-MYC EXPRESSION; CELL IDENTITY; GENOME-WIDE; BET BROMODOMAIN; DNA ELEMENTS; SELECTIVE-INHIBITION; GENETIC DISSECTION;
D O I
10.3390/cells12081191
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页数:33
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