Functional modularity of nuclear hormone receptors in a Caenorhabditis elegans metabolic gene regulatory network

Abstract Gene regulatory networks (GRNs) provide insights into the mechanisms of differential gene expression at a systems level. GRNs that relate to metazoan development have been studied extensively. However, little is still known about the design principles, organization and functionality of GRNs...

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Main Authors: H Efsun Arda, Stefan Taubert, Lesley T MacNeil, Colin C Conine, Ben Tsuda, Marc Van Gilst, Reynaldo Sequerra, Lynn Doucette‐Stamm, Keith R Yamamoto, Albertha J M Walhout
Format: Article
Language:English
Published: Springer Nature 2010-05-01
Series:Molecular Systems Biology
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Online Access:https://doi.org/10.1038/msb.2010.23
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author H Efsun Arda
Stefan Taubert
Lesley T MacNeil
Colin C Conine
Ben Tsuda
Marc Van Gilst
Reynaldo Sequerra
Lynn Doucette‐Stamm
Keith R Yamamoto
Albertha J M Walhout
author_facet H Efsun Arda
Stefan Taubert
Lesley T MacNeil
Colin C Conine
Ben Tsuda
Marc Van Gilst
Reynaldo Sequerra
Lynn Doucette‐Stamm
Keith R Yamamoto
Albertha J M Walhout
author_sort H Efsun Arda
collection DOAJ
description Abstract Gene regulatory networks (GRNs) provide insights into the mechanisms of differential gene expression at a systems level. GRNs that relate to metazoan development have been studied extensively. However, little is still known about the design principles, organization and functionality of GRNs that control physiological processes such as metabolism, homeostasis and responses to environmental cues. In this study, we report the first experimentally mapped metazoan GRN of Caenorhabditis elegans metabolic genes. This network is enriched for nuclear hormone receptors (NHRs). The NHR family has greatly expanded in nematodes: humans have 48 NHRs, but C. elegans has 284, most of which are uncharacterized. We find that the C. elegans metabolic GRN is highly modular and that two GRN modules predominantly consist of NHRs. Network modularity has been proposed to facilitate a rapid response to different cues. As NHRs are metabolic sensors that are poised to respond to ligands, this suggests that C. elegans GRNs evolved to enable rapid and adaptive responses to different cues by a concurrence of NHR family expansion and modular GRN wiring.
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spelling doaj-art-3a65b7317a6a45a985811f7268e68db32025-08-24T12:00:42ZengSpringer NatureMolecular Systems Biology1744-42922010-05-016111410.1038/msb.2010.23Functional modularity of nuclear hormone receptors in a Caenorhabditis elegans metabolic gene regulatory networkH Efsun Arda0Stefan Taubert1Lesley T MacNeil2Colin C Conine3Ben Tsuda4Marc Van Gilst5Reynaldo Sequerra6Lynn Doucette‐Stamm7Keith R Yamamoto8Albertha J M Walhout9Program in Gene Function and Expression and Program in Molecular Medicine, University of Massachusetts Medical SchoolDepartment of Cellular and Molecular Pharmacology, University of CaliforniaProgram in Gene Function and Expression and Program in Molecular Medicine, University of Massachusetts Medical SchoolProgram in Gene Function and Expression and Program in Molecular Medicine, University of Massachusetts Medical SchoolProgram in Gene Function and Expression and Program in Molecular Medicine, University of Massachusetts Medical SchoolBasic Sciences Division, Fred Hutchinson Cancer Research CenterAgencourt Bioscience CorporationAgencourt Bioscience CorporationDepartment of Cellular and Molecular Pharmacology, University of CaliforniaProgram in Gene Function and Expression and Program in Molecular Medicine, University of Massachusetts Medical SchoolAbstract Gene regulatory networks (GRNs) provide insights into the mechanisms of differential gene expression at a systems level. GRNs that relate to metazoan development have been studied extensively. However, little is still known about the design principles, organization and functionality of GRNs that control physiological processes such as metabolism, homeostasis and responses to environmental cues. In this study, we report the first experimentally mapped metazoan GRN of Caenorhabditis elegans metabolic genes. This network is enriched for nuclear hormone receptors (NHRs). The NHR family has greatly expanded in nematodes: humans have 48 NHRs, but C. elegans has 284, most of which are uncharacterized. We find that the C. elegans metabolic GRN is highly modular and that two GRN modules predominantly consist of NHRs. Network modularity has been proposed to facilitate a rapid response to different cues. As NHRs are metabolic sensors that are poised to respond to ligands, this suggests that C. elegans GRNs evolved to enable rapid and adaptive responses to different cues by a concurrence of NHR family expansion and modular GRN wiring.https://doi.org/10.1038/msb.2010.23C. elegansgene regulatory networkmetabolismnuclear hormone receptortranscription factor
spellingShingle H Efsun Arda
Stefan Taubert
Lesley T MacNeil
Colin C Conine
Ben Tsuda
Marc Van Gilst
Reynaldo Sequerra
Lynn Doucette‐Stamm
Keith R Yamamoto
Albertha J M Walhout
Functional modularity of nuclear hormone receptors in a Caenorhabditis elegans metabolic gene regulatory network
Molecular Systems Biology
C. elegans
gene regulatory network
metabolism
nuclear hormone receptor
transcription factor
title Functional modularity of nuclear hormone receptors in a Caenorhabditis elegans metabolic gene regulatory network
title_full Functional modularity of nuclear hormone receptors in a Caenorhabditis elegans metabolic gene regulatory network
title_fullStr Functional modularity of nuclear hormone receptors in a Caenorhabditis elegans metabolic gene regulatory network
title_full_unstemmed Functional modularity of nuclear hormone receptors in a Caenorhabditis elegans metabolic gene regulatory network
title_short Functional modularity of nuclear hormone receptors in a Caenorhabditis elegans metabolic gene regulatory network
title_sort functional modularity of nuclear hormone receptors in a caenorhabditis elegans metabolic gene regulatory network
topic C. elegans
gene regulatory network
metabolism
nuclear hormone receptor
transcription factor
url https://doi.org/10.1038/msb.2010.23
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