{"title":"Liver gene regulatory networks: Contributing factors to nonalcoholic fatty liver disease.","authors":"Inês Cebola","doi":"10.1002/wsbm.1480","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":49254,"journal":{"name":"Wiley Interdisciplinary Reviews-Systems Biology and Medicine","volume":"12 3","pages":"e1480"},"PeriodicalIF":7.9000,"publicationDate":"2020-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/wsbm.1480","citationCount":"1","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Wiley Interdisciplinary Reviews-Systems Biology and Medicine","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1002/wsbm.1480","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2020/2/4 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"Medicine","Score":null,"Total":0}
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.
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