title: Genome-wide identification of binding sites defines distinct functions for Caenorhabditis elegans PHA-4/FOXA in development and environmental response.
abstract: Transcription factors are key components of regulatory networks that control development, as well as the response to environmental stimuli. We have established an experimental pipeline in Caenorhabditis elegans that permits global identification of the binding sites for transcription factors using chromatin immunoprecipitation and deep sequencing. We describe and validate this strategy, and apply it to the transcription factor PHA-4, which plays critical roles in organ development and other cellular processes. We identified thousands of binding sites for PHA-4 during formation of the embryonic pharynx, and also found a role for this factor during the starvation response. Many binding sites were found to shift dramatically between embryos and starved larvae, from developmentally regulated genes to genes involved in metabolism. These results indicate distinct roles for this regulator in two different biological processes and demonstrate the versatility of transcription factors in mediating diverse biological roles.
authors.affiliation: Department of Molecular Cellular Developmental Biology, Yale University, New Haven, Connecticut, United States of America.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhong
authors.forename: Wei
authors.initials: W
authors.lastname: Niu
authors.forename: Zhi John
authors.initials: ZJ
authors.lastname: Lu
authors.forename: Mihail
authors.initials: M
authors.lastname: Sarov
authors.forename: John I
authors.initials: JI
authors.lastname: Murray
authors.forename: Judith
authors.initials: J
authors.lastname: Janette
authors.forename: Debasish
authors.initials: D
authors.lastname: Raha
authors.forename: Karyn L
authors.initials: KL
authors.lastname: Sheaffer
authors.forename: Hugo Y K
authors.initials: HY
authors.lastname: Lam
authors.forename: Elicia
authors.initials: E
authors.lastname: Preston
authors.forename: Cindie
authors.initials: C
authors.lastname: Slightham
authors.forename: LaDeana W
authors.initials: LW
authors.lastname: Hillier
authors.forename: Trisha
authors.initials: T
authors.lastname: Brock
authors.forename: Ashish
authors.initials: A
authors.lastname: Agarwal
authors.forename: Raymond
authors.initials: R
authors.lastname: Auerbach
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Hyman
authors.forename: Mark
authors.initials: M
authors.lastname: Gerstein
authors.forename: Susan E
authors.initials: SE
authors.lastname: Mango
authors.forename: Stuart K
authors.initials: SK
authors.lastname: Kim
authors.forename: Robert H
authors.initials: RH
authors.lastname: Waterston
authors.forename: Valerie
authors.initials: V
authors.lastname: Reinke
authors.forename: Michael
authors.initials: M
authors.lastname: Snyder
mesh_terms: D000818:Animals; D001665:Binding Sites; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000254:growth & development*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D004625:Embryo, Nonmammalian / Q000378:metabolism; D004777:Environment; D018507:Gene Expression Regulation, Developmental; D017238:Genes, Helminth / Q000235:genetics; D049751:Genome, Helminth / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007814:Larva / Q000378:metabolism; D011485:Protein Binding; D012319:RNA Polymerase II / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013217:Starvation; D016019:Survival Analysis; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; C113277:Pha-4 protein, C elegans; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; D012319:RNA Polymerase II