title: A gene-centered C. elegans protein-DNA interaction network provides a framework for functional predictions.
abstract: Transcription factors (TFs) play a central role in controlling spatiotemporal gene expression and the response to environmental cues. A comprehensive understanding of gene regulation requires integrating physical protein-DNA interactions (PDIs) with TF regulatory activity, expression patterns, and phenotypic data. Although great progress has been made in mapping PDIs using chromatin immunoprecipitation, these studies have only characterized ~10% of TFs in any metazoan species. The nematode C. elegans has been widely used to study gene regulation due to its compact genome with short regulatory sequences. Here, we delineated the largest gene-centered metazoan PDI network to date by examining interactions between 90% of C. elegans TFs and 15% of gene promoters. We used this network as a backbone to predict TF binding sites for 77 TFs, two-thirds of which are novel, as well as integrate gene expression, protein-protein interaction, and phenotypic data to predict regulatory and biological functions for multiple genes and TFs.
authors: Program in Systems Biology and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
authors: Juan I
authors: JI
authors: Fuxman Bass
authors: Department of Computer Science and Engineering, University of Minnesota-Twin Cities, Minneapolis, MN, USA.
authors: Carles
authors: C
authors: Pons
authors: Program in Systems Biology and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
authors: Lucie
authors: L
authors: Kozlowski
authors: Program in Systems Biology and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
authors: John S
authors: JS
authors: Reece-Hoyes
authors: Program in Systems Biology and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
authors: Shaleen
authors: S
authors: Shrestha
authors: Program in Systems Biology and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
authors: Amy D
authors: AD
authors: Holdorf
authors: Program in Systems Biology and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
authors: Akihiro
authors: A
authors: Mori
authors: Department of Computer Science and Engineering, University of Minnesota-Twin Cities, Minneapolis, MN, USA.
authors: Chad L
authors: CL
authors: Myers
authors: Program in Systems Biology and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA marian.walhout@umassmed.edu.
authors: Albertha Jm
authors: http://orcid.org/0000-0001-5587-3608
authors: AJ
authors: Walhout
mesh_terms: D000818:Animals; D001665:Binding Sites; D017173:Caenorhabditis elegans / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000378:metabolism; D005786:Gene Expression Regulation; D011485:Protein Binding; D060066:Protein Interaction Maps; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism*; D016053:RNA, Protozoan / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D012333:RNA, Messenger; D016053:RNA, Protozoan; D014157:Transcription Factors
keywords: 
  C. elegans
  ; gene regulation; protein–DNA interaction network; transcription factors; yeast one‐hybrid assays