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Nature. 2014 Aug 28;512(7515):453-6. doi: 10.1038/nature13668.

Comparative analysis of regulatory information and circuits across distant species.

Author information

1
1] Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA [2].
2
Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA.
3
Program of Computational Biology and Bioinformatics, Yale University, New Haven, Connecticut 06520, USA.
4
Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
5
Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA.
6
Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
7
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.
8
1] Department of Statistics, University of California, Berkeley, California 94720, USA [2] Department of Statistics, University of California, Los Angeles, California 90095, USA.
9
Institute for Genomics and Systems Biology, University of Chicago, Chicago, Ilinois 60637, USA.
10
National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, 20892, USA.
11
Department of Statistics, University of California, Berkeley, California 94720, USA.
12
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.

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.

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PMID:
25164757
PMCID:
PMC4336544
DOI:
10.1038/nature13668
[Indexed for MEDLINE]
Free PMC Article

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