title: Comparative analysis of regulatory information and circuits across distant species.
abstract: Despite the large evolutionary distances between metazoan species, they can show remarkable commonalities in their biology, and this has helped to establish fly and worm as model organisms for human biology. Although studies of individual elements and factors have explored similarities in gene regulation, a large-scale comparative analysis of basic principles of transcriptional regulatory features is lacking. Here we map the genome-wide binding locations of 165 human, 93 worm and 52 fly transcription regulatory factors, generating a total of 1,019 data sets from diverse cell types, developmental stages, or conditions in the three species, of which 498 (48.9%) are presented here for the first time. We find that structural properties of regulatory networks are remarkably conserved and that orthologous regulatory factor families recognize similar binding motifs in vivo and show some similar co-associations. Our results suggest that gene-regulatory properties previously observed for individual factors are general principles of metazoan regulation that are remarkably well-preserved despite extensive functional divergence of individual network connections. The comparative maps of regulatory circuitry provided here will drive an improved understanding of the regulatory underpinnings of model organism biology and how these relate to human biology, development and disease.
authors.affiliation: 1] Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA [2].
authors.forename: Alan P
authors.initials: AP
authors.lastname: Boyle
authors.affiliation: 1] Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA [2].
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: Cathleen
authors.initials: C
authors.lastname: Brdlik
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Philip
authors.initials: P
authors.lastname: Cayting
authors.affiliation: Program of Computational Biology and Bioinformatics, Yale University, New Haven, Connecticut 06520, USA.
authors.forename: Chao
authors.initials: C
authors.lastname: Cheng
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Gardner
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA.
authors.forename: LaDeana W
authors.initials: LW
authors.lastname: Hillier
authors.affiliation: Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
authors.forename: Judith
authors.initials: J
authors.lastname: Janette
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, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
authors.forename: Dionna
authors.initials: D
authors.lastname: Kasper
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: Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Pouya
authors.initials: P
authors.lastname: Kheradpour
authors.affiliation: 1] Department of Computer Science, Stanford University, Stanford, California 94305, USA [2] Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Anshul
authors.initials: A
authors.lastname: Kundaje
authors.affiliation: 1] Department of Statistics, University of California, Berkeley, California 94720, USA [2] Department of Statistics, University of California, Los Angeles, California 90095, USA.
authors.forename: Jingyi Jessica
authors.initials: JJ
authors.lastname: Li
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Lijia
authors.initials: L
authors.lastname: Ma
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: Institute for Genomics and Systems Biology, University of Chicago, Chicago, Ilinois 60637, USA.
authors.forename: E Jay
authors.initials: EJ
authors.lastname: Rehm
authors.affiliation: Program of Computational Biology and Bioinformatics, Yale University, New Haven, Connecticut 06520, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Rozowsky
authors.affiliation: Institute for Genomics and Systems Biology, University of Chicago, Chicago, Ilinois 60637, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Slattery
authors.affiliation: Institute for Genomics and Systems Biology, University of Chicago, Chicago, Ilinois 60637, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Spokony
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: Dionne
authors.initials: D
authors.lastname: Vafeados
authors.affiliation: Program of Computational Biology and Bioinformatics, Yale University, New Haven, Connecticut 06520, USA.
authors.forename: Daifeng
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Weisdepp
authors.affiliation: Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Yi-Chieh
authors.initials: YC
authors.lastname: Wu
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: Program of Computational Biology and Bioinformatics, Yale University, New Haven, Connecticut 06520, USA.
authors.forename: Koon-Kiu
authors.initials: KK
authors.lastname: Yan
authors.affiliation: National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, 20892, USA.
authors.forename: Elise A
authors.initials: EA
authors.lastname: Feingold
authors.affiliation: National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, 20892, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Good
authors.affiliation: National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, 20892, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Pazin
authors.affiliation: Department of Statistics, University of California, Berkeley, California 94720, USA.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Statistics, University of California, Berkeley, California 94720, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Bickel
authors.affiliation: 1] Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA [2] Department of Plant and Microbial Biology, University of California, Berkeley, California 94720, USA.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Brenner
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: Program of Computational Biology and Bioinformatics, Yale University, New Haven, Connecticut 06520, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Gerstein
authors.affiliation: Institute for Genomics and Systems Biology, University of Chicago, Chicago, Ilinois 60637, USA.
authors.forename: Kevin P
authors.initials: KP
authors.lastname: White
authors.affiliation: Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Manolis
authors.initials: M
authors.lastname: Kellis
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 / Q000235:genetics* / Q000254:growth & development; D047369:Chromatin Immunoprecipitation; D017124:Conserved Sequence / Q000235:genetics; D004331:Drosophila melanogaster / Q000235:genetics* / Q000254:growth & development; D019143:Evolution, Molecular; D005786:Gene Expression Regulation / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D053263:Gene Regulatory Networks / Q000235:genetics*; D016678:Genome / Q000235:genetics; D006801:Humans; D058977:Molecular Sequence Annotation; D059372:Nucleotide Motifs / Q000235:genetics; D009928:Organ Specificity / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D014157:Transcription Factors