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超级增强子及其组成部分:从预测努力到特征状态。

Super-Enhancers and Their Parts: From Prediction Efforts to Pathognomonic Status.

机构信息

Prokhorov General Physics Institute of the Russian Academy of Sciences, 38 Vavilov St., 119991 Moscow, Russia.

Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, GSP-1, Leninskiye Gory, MSU, 1-73, 119234 Moscow, Russia.

出版信息

Int J Mol Sci. 2024 Mar 7;25(6):3103. doi: 10.3390/ijms25063103.


DOI:10.3390/ijms25063103
PMID:38542080
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10969950/
Abstract

Super-enhancers (SEs) are regions of the genome that play a crucial regulatory role in gene expression by promoting large-scale transcriptional responses in various cell types and tissues. Recent research suggests that alterations in super-enhancer activity can contribute to the development and progression of various disorders. The aim of this research is to explore the multifaceted roles of super-enhancers in gene regulation and their significant implications for understanding and treating complex diseases. Here, we study and summarise the classification of super-enhancer constituents, their possible modes of interaction, and cross-regulation, including super-enhancer RNAs (seRNAs). We try to investigate the opportunity of SE dynamics prediction based on the hierarchy of enhancer single elements (enhancers) and their aggregated action. To further our understanding, we conducted an in silico experiment to compare and differentiate between super-enhancers and locus-control regions (LCRs), shedding light on the enigmatic relationship between LCRs and SEs within the human genome. Particular attention is paid to the classification of specific mechanisms and their diversity, exemplified by various oncological, cardiovascular, and immunological diseases, as well as an overview of several anti-SE therapies. Overall, the work presents a comprehensive analysis of super-enhancers across different diseases, aiming to provide insights into their regulatory roles and may act as a rationale for future clinical interventions targeting these regulatory elements.

摘要

超级增强子(SEs)是基因组中的区域,通过在各种细胞类型和组织中促进大规模转录反应,在基因表达中发挥着关键的调节作用。最近的研究表明,超级增强子活性的改变可能导致各种疾病的发生和发展。本研究旨在探讨超级增强子在基因调控中的多方面作用及其对理解和治疗复杂疾病的重要意义。在这里,我们研究和总结了超级增强子成分的分类、它们可能的相互作用模式和交叉调节,包括超级增强子 RNA(seRNA)。我们试图探讨基于增强子单个元件(增强子)的层次结构及其聚合作用来预测 SE 动态的可能性。为了进一步深入了解,我们进行了一项计算机模拟实验,比较和区分超级增强子和位置控制区(LCRs),揭示了人类基因组中 LCRs 和 SEs 之间神秘的关系。特别关注特定机制的分类及其多样性,包括各种肿瘤、心血管和免疫学疾病,并概述了几种抗 SE 治疗方法。总的来说,这项工作对不同疾病中的超级增强子进行了全面分析,旨在深入了解它们的调节作用,并为未来针对这些调节元件的临床干预提供依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f531/10969950/ee9afc1b7e31/ijms-25-03103-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f531/10969950/9dfd99950a59/ijms-25-03103-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f531/10969950/da28ad6c2e3b/ijms-25-03103-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f531/10969950/509c27790fdf/ijms-25-03103-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f531/10969950/e5a6beb9d3c1/ijms-25-03103-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f531/10969950/e15a6a630db6/ijms-25-03103-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f531/10969950/d20d8cc14b83/ijms-25-03103-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f531/10969950/ee9afc1b7e31/ijms-25-03103-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f531/10969950/9dfd99950a59/ijms-25-03103-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f531/10969950/da28ad6c2e3b/ijms-25-03103-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f531/10969950/509c27790fdf/ijms-25-03103-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f531/10969950/e5a6beb9d3c1/ijms-25-03103-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f531/10969950/e15a6a630db6/ijms-25-03103-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f531/10969950/d20d8cc14b83/ijms-25-03103-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f531/10969950/ee9afc1b7e31/ijms-25-03103-g007.jpg

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[1]
Quantitative Rapid Magnetic Immunoassay for Sensitive Toxin Detection in Food: Non-Covalent Functionalization of Nanolabels vs. Covalent Immobilization.

Toxins (Basel). 2023-12-20

[2]
Efficient Chlorostannate Modification of Magnetite Nanoparticles for Their Biofunctionalization.

Materials (Basel). 2024-1-10

[3]
Super-enhancers include classical enhancers and facilitators to fully activate gene expression.

Cell. 2023-12-21

[4]
JUN-induced super-enhancer RNA forms R-loop to promote nasopharyngeal carcinoma metastasis.

Cell Death Dis. 2023-7-21

[5]
Super Enhancer Driven Hyaluronan Synthase 3 Promotes Malignant Progression of Nasopharyngeal Carcinoma.

J Cancer. 2023-6-12

[6]
Super-enhancer-driven MLX mediates redox balance maintenance via SLC7A11 in osteosarcoma.

Cell Death Dis. 2023-7-17

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Super-enhancer-associated gene CAPG promotes AML progression.

Commun Biol. 2023-6-9

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Nucleic Acids Res. 2023-7-5

[9]
Topologically associating domain boundaries are required for normal genome function.

Commun Biol. 2023-4-20

[10]
LSD1 Inhibition Disrupts Super-Enhancer-Driven Oncogenic Transcriptional Programs in Castration-Resistant Prostate Cancer.

Cancer Res. 2023-5-15

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