title: Transcription Factor Activity Mapping of a Tissue-Specificin vivoGene Regulatory Network.
abstract: A wealth of physical interaction data between transcription factors (TFs) and DNA has been generated, but these interactions often do not have apparent regulatory consequences. Thus, equating physical interaction data with gene regulatory networks (GRNs) is problematic. Here, we comprehensively assay TF activity, rather than binding, to construct a network of gene regulatory interactions in theC. elegansintestine. By manually observing thein vivotissue-specific knockdown of 921 TFs on a panel of 19 fluorescent transcriptional reporters, we identified a GRN of 411 interactions between 19 promoters and 177 TFs. This GRN shows only modest overlap with physical interactions, indicating that many regulatory interactions are indirect. We applied nested effects modeling to uncover information flow between TFs in the intestine that converges on a small set of physical TF-promoter interactions. We found numerous cell nonautonomous regulatory interactions, illustrating tissue-to-tissue communication. Altogether, our study illuminates the complexity of gene regulation in the context of a living animal.
authors.affiliation: Program in Systems Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA ; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Lesley T
authors.initials: LT
authors.lastname: MacNeil
authors.affiliation: Department of Computer Science and Engineering, University of Minnesota-Twin Cities, Minneapolis, MN 55455, USA.
authors.forename: Carles
authors.initials: C
authors.lastname: Pons
authors.affiliation: Program in Systems Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA ; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: H Efsun
authors.initials: HE
authors.lastname: Arda
authors.affiliation: Program in Systems Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Gabrielle E
authors.initials: GE
authors.lastname: Giese
authors.affiliation: Department of Computer Science and Engineering, University of Minnesota-Twin Cities, Minneapolis, MN 55455, USA.
authors.forename: Chad L
authors.initials: CL
authors.lastname: Myers
authors.affiliation: Program in Systems Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA ; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Albertha J M
authors.initials: AJ
authors.lastname: Walhout