Liver gene regulatory networks: Contributing factors to nonalcoholic fatty liver disease.

IF 7.9 Q1 Medicine Wiley Interdisciplinary Reviews-Systems Biology and Medicine Pub Date : 2020-05-01 Epub Date: 2020-02-04 DOI:10.1002/wsbm.1480
Inês Cebola
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引用次数: 1

Abstract

Metabolic diseases such as nonalcoholic fatty liver disease (NAFLD) result from complex interactions between intrinsic and extrinsic factors, including genetics and exposure to obesogenic environments. These risk factors converge in aberrant gene expression patterns in the liver, which are underlined by altered cis-regulatory networks. In homeostasis and in disease states, liver cis-regulatory networks are established by coordinated action of liver-enriched transcription factors (TFs), which define enhancer landscapes, activating broad gene programs with spatiotemporal resolution. Recent advances in DNA sequencing have dramatically expanded our ability to map active transcripts, enhancers and TF cistromes, and to define the 3D chromatin topology that contains these elements. Deployment of these technologies has allowed investigation of the molecular processes that regulate liver development and metabolic homeostasis. Moreover, genomic studies of NAFLD patients and NAFLD models have demonstrated that the liver undergoes pervasive regulatory rewiring in NAFLD, which is reflected by aberrant gene expression profiles. We have therefore achieved an unprecedented level of detail in the understanding of liver cis-regulatory networks, particularly in physiological conditions. Future studies should aim to map active regulatory elements with added levels of resolution, addressing how the chromatin landscapes of different cell lineages contribute to and are altered in NAFLD and NAFLD-associated metabolic states. Such efforts would provide additional clues into the molecular factors that trigger this disease. This article is categorized under: Biological Mechanisms > Metabolism Biological Mechanisms > Regulatory Biology Laboratory Methods and Technologies > Genetic/Genomic Methods.

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肝脏基因调控网络:非酒精性脂肪性肝病的影响因素
代谢性疾病,如非酒精性脂肪性肝病(NAFLD)是由内在和外在因素(包括遗传和暴露于致肥环境)之间复杂的相互作用引起的。这些危险因素集中在肝脏中异常的基因表达模式,这是由改变的顺式调控网络所强调的。在体内平衡和疾病状态下,肝脏顺式调控网络是通过肝脏富集转录因子(TFs)的协调作用建立的,这些转录因子定义了增强子景观,激活了具有时空分辨率的广泛基因程序。DNA测序的最新进展极大地扩展了我们绘制活性转录本、增强子和TF基质的能力,并定义了包含这些元素的三维染色质拓扑结构。这些技术的应用使得研究调节肝脏发育和代谢稳态的分子过程成为可能。此外,对NAFLD患者和NAFLD模型的基因组研究表明,在NAFLD中,肝脏经历了普遍的调控重布线,这反映在异常的基因表达谱上。因此,我们在理解肝脏顺式调节网络方面,特别是在生理条件下,达到了前所未有的详细水平。未来的研究应旨在以更高的分辨率绘制活性调控元件,解决不同细胞系的染色质景观如何促进NAFLD和NAFLD相关代谢状态的改变。这些努力将为了解引发这种疾病的分子因素提供更多线索。本文分类如下:生物学机制>代谢生物学机制>调控生物学实验室方法和技术>遗传/基因组方法。
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CiteScore
18.40
自引率
0.00%
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0
审稿时长
>12 weeks
期刊介绍: Journal Name:Wiley Interdisciplinary Reviews-Systems Biology and Medicine Focus: Strong interdisciplinary focus Serves as an encyclopedic reference for systems biology research Conceptual Framework: Systems biology asserts the study of organisms as hierarchical systems or networks Individual biological components interact in complex ways within these systems Article Coverage: Discusses biology, methods, and models Spans systems from a few molecules to whole species Topical Coverage: Developmental Biology Physiology Biological Mechanisms Models of Systems, Properties, and Processes Laboratory Methods and Technologies Translational, Genomic, and Systems Medicine
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