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

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.

Pubmed ID: 20461074


  • Arda HE
  • Taubert S
  • MacNeil LT
  • Conine CC
  • Tsuda B
  • Van Gilst M
  • Sequerra R
  • Doucette-Stamm L
  • Yamamoto KR
  • Walhout AJ


Molecular systems biology

Publication Data

May 11, 2010

Associated Grants

  • Agency: NIDDK NIH HHS, Id: 5 P30 DK32520
  • Agency: NCI NIH HHS, Id: CA020535
  • Agency: NIDDK NIH HHS, Id: DK068429
  • Agency: NIDDK NIH HHS, Id: DK071713
  • Agency: NIDDK NIH HHS, Id: DK32520
  • Agency: NIDDK NIH HHS, Id: R01 DK068429

Mesh Terms

  • Animals
  • Caenorhabditis elegans
  • Gene Expression Regulation
  • Gene Regulatory Networks
  • Models, Genetic
  • Promoter Regions, Genetic
  • RNA Interference
  • Receptors, Cytoplasmic and Nuclear
  • Two-Hybrid System Techniques
  • Yeasts