title: 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 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.
authors.affiliation: Program in Gene Function and Expression and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: H Efsun
authors.initials: HE
authors.lastname: Arda
authors.forename: Stefan
authors.initials: S
authors.lastname: Taubert
authors.forename: Lesley T
authors.initials: LT
authors.lastname: MacNeil
authors.forename: Colin C
authors.initials: CC
authors.lastname: Conine
authors.forename: Ben
authors.initials: B
authors.lastname: Tsuda
authors.forename: Marc
authors.initials: M
authors.lastname: Van Gilst
authors.forename: Reynaldo
authors.initials: R
authors.lastname: Sequerra
authors.forename: Lynn
authors.initials: L
authors.lastname: Doucette-Stamm
authors.forename: Keith R
authors.initials: KR
authors.lastname: Yamamoto
authors.forename: Albertha J M
authors.initials: AJ
authors.lastname: Walhout
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks / Q000235:genetics*; D008957:Models, Genetic; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D015003:Yeasts
chemical_list: D018160:Receptors, Cytoplasmic and Nuclear
references.citation: Trends Genet. 2005 Jan;21(1):16-20
references.pmid: 15680508
references.citation: Genome Biol. 2005;6(13):R110
references.pmid: 16420670
references.citation: Methods. 2001 Jul;24(3):297-306
references.pmid: 11403578
references.citation: Genes Dev. 2009 Feb 15;23(4):496-511
references.pmid: 19240135
references.citation: Nat Methods. 2007 Aug;4(8):659-64
references.pmid: 17589517
references.citation: PLoS Biol. 2007 Sep;5(9):e237
references.pmid: 17850180
references.citation: Cell Metab. 2008 Aug;8(2):105-17
references.pmid: 18680712
references.citation: BMC Genomics. 2008 Aug 27;9:399
references.pmid: 18752680
references.citation: Science. 2002 Oct 25;298(5594):824-7
references.pmid: 12399590
references.citation: Cell Metab. 2005 Jun;1(6):361-70
references.pmid: 16054085
references.citation: Dev Biol. 2002 Jun 1;246(1):68-85
references.pmid: 12027435
references.citation: Genome Res. 2006 Dec;16(12):1445-54
references.pmid: 17053092
references.citation: Science. 2009 Apr 3;324(5923):92-4
references.pmid: 19251593
references.citation: Cell. 2006 Mar 24;124(6):1209-23
references.pmid: 16529801
references.citation: Mol Biol Cell. 2007 Mar;18(3):995-1008
references.pmid: 17202409
references.citation: CSH Protoc. 2006 Oct 01;2006(5):
references.pmid: 22485967
references.citation: Genome Res. 2004 Oct;14(10B):2093-101
references.pmid: 15489331
references.citation: Genes Dev. 2008 Sep 15;22(18):2535-49
references.pmid: 18794350
references.citation: Nature. 1996 Dec 5;384(6608):458-60
references.pmid: 8945471
references.citation: PLoS Biol. 2005 Feb;3(2):e53
references.pmid: 15719061
references.citation: Nature. 2003 Jan 16;421(6920):268-72
references.pmid: 12529643
references.citation: Nat Rev Genet. 2007 Jun;8(6):450-61
references.pmid: 17510665
references.citation: PLoS Genet. 2006 Jul;2(7):e108
references.pmid: 16839188
references.citation: Annu Rev Genomics Hum Genet. 2006;7:81-102
references.pmid: 16722805
references.citation: Genes Dev. 2000 Jun 15;14(12):1512-27
references.pmid: 10859169
references.citation: Genes Dev. 2009 Feb 15;23(4):419-32
references.pmid: 19240130
references.citation: Genes Dev. 2007 Feb 15;21(4):436-49
references.pmid: 17322403
references.citation: Genome Res. 2007 Jul;17(7):1061-71
references.pmid: 17513831
references.citation: Trends Endocrinol Metab. 2008 Jul;19(5):153-60
references.pmid: 18406164
references.citation: Nat Genet. 2003 Jun;34(2):166-76
references.pmid: 12740579
references.citation: Science. 2001 Nov 30;294(5548):1866-70
references.pmid: 11729302
references.citation: Proc Natl Acad Sci U S A. 2008 Dec 23;105(51):20095-9
references.pmid: 19104047
references.citation: Nat Rev Genet. 2009 Apr;10(4):252-63
references.pmid: 19274049
references.citation: Proc Natl Acad Sci U S A. 2005 Apr 5;102(14):4935
references.pmid: 15809445
references.citation: BMC Genomics. 2007 Jan 18;8:21
references.pmid: 17233892
references.citation: Science. 2002 Aug 30;297(5586):1551-5
references.pmid: 12202830
references.citation: Genome Res. 2003 Nov;13(11):2498-504
references.pmid: 14597658
references.citation: PLoS Genet. 2008 Feb 29;4(2):e1000021
references.pmid: 18454197
references.citation: Nature. 2003 Jan 16;421(6920):231-7
references.pmid: 12529635
references.citation: BMC Genomics. 2007 Jan 23;8:27
references.pmid: 17244357
references.citation: Cell. 2009 Jul 23;138(2):314-27
references.pmid: 19632181
references.citation: Genome Biol. 2001;2(8):RESEARCH0029
references.pmid: 11532213
references.citation: Nat Genet. 2007 Dec;39(12):1512-6
references.pmid: 17994019
references.citation: Mol Syst Biol. 2006;2:2006.0017
references.pmid: 16738562
references.citation: Science. 2000 Jan 7;287(5450):116-22
references.pmid: 10615043
references.citation: Genetics. 1974 May;77(1):71-94
references.pmid: 4366476
references.citation: Genome Res. 2004 Oct;14(10B):2169-75
references.pmid: 15489340
references.citation: Curr Opin Struct Biol. 2004 Jun;14(3):283-91
references.pmid: 15193307
references.citation: Cell Metab. 2008 Jun;7(6):533-44
references.pmid: 18522834
references.citation: EMBO J. 1991 Dec;10(12):3959-70
references.pmid: 1935914
references.citation: Cell. 2006 Jun 16;125(6):1193-205
references.pmid: 16777607
references.citation: Genes Dev. 2006 May 1;20(9):1137-49
references.pmid: 16651656
references.citation: Methods Enzymol. 2000;328:575-92
references.pmid: 11075367
references.citation: Cell Metab. 2009 Mar;9(3):228-39
references.pmid: 19254568
references.citation: Genome Res. 2004 Oct;14(10B):2162-8
references.pmid: 15489339
references.citation: PLoS Biol. 2008 Feb;6(2):e27
references.pmid: 18271625
references.citation: Nature. 2006 Aug 10;442(7103):700-4
references.pmid: 16799563
references.citation: Development. 2005 Apr;132(8):1843-54
references.pmid: 15772128
references.citation: Genetics. 2008 Oct;180(2):857-71
references.pmid: 18780725
references.citation: Science. 2002 Mar 1;295(5560):1669-78
references.pmid: 11872831
references.citation: Nucleic Acids Res. 2009 Jun;37(11):3689-98
references.pmid: 19372275
references.citation: Brief Funct Genomics. 2010 Jan;9(1):4-12
references.pmid: 20008400
references.citation: Proc Natl Acad Sci U S A. 2005 Sep 20;102(38):13496-501
references.pmid: 16157872
references.citation: Nature. 2004 Sep 2;431(7004):99-104
references.pmid: 15343339
references.citation: Nat Genet. 2003 May;34(1):35-41
references.pmid: 12679813