title: Regulatory analysis of the C. elegans genome with spatiotemporal resolution.
abstract: Discovering the structure and dynamics of transcriptional regulatory events in the genome with cellular and temporal resolution is crucial to understanding the regulatory underpinnings of development and disease. We determined the genomic distribution of binding sites for 92 transcription factors and regulatory proteins across multiple stages of Caenorhabditis elegans development by performing 241 ChIP-seq (chromatin immunoprecipitation followed by sequencing) experiments. Integration of regulatory binding and cellular-resolution expression data produced a spatiotemporally resolved metazoan transcription factor binding map. Using this map, we explore developmental regulatory circuits that encode combinatorial logic at the levels of co-binding and co-expression of transcription factors, characterizing the genomic coverage and clustering of regulatory binding, the binding preferences of, and biological processes regulated by, transcription factors, the global transcription factor co-associations and genomic subdomains that suggest shared patterns of regulation, and identifying key transcription factors and transcription factor co-associations for fate specification of individual lineages and cell types.
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Carlos L
authors.initials: CL
authors.lastname: Araya
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Trupti
authors.initials: T
authors.lastname: Kawli
authors.affiliation: Department of Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Anshul
authors.initials: A
authors.lastname: Kundaje
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Lixia
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Beijing
authors.initials: B
authors.lastname: Wu
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Dionne
authors.initials: D
authors.lastname: Vafeados
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Terrell
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Weissdepp
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Louis
authors.initials: L
authors.lastname: Gevirtzman
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Mace
authors.affiliation: Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Niu
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Alan P
authors.initials: AP
authors.lastname: Boyle
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Xie
authors.affiliation: Institute for Genomics and Systems Biology, University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Lijia
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: John I
authors.initials: JI
authors.lastname: Murray
authors.affiliation: Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
authors.forename: Valerie
authors.initials: V
authors.lastname: Reinke
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Waterston
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Snyder
mesh_terms: D000818:Animals; D001665:Binding Sites; D017173:Caenorhabditis elegans / Q000166:cytology / Q000196:embryology / Q000235:genetics* / Q000254:growth & development*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D019070:Cell Lineage; D047369:Chromatin Immunoprecipitation; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D049751:Genome, Helminth / Q000235:genetics*; D023281:Genomics; D007814:Larva / Q000166:cytology / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D011485:Protein Binding; D062211:Spatio-Temporal Analysis; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D014157:Transcription Factors