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A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping.

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      Abstract

      We use in situ Hi-C to probe the 3D architecture of genomes, constructing haploid and diploid maps of nine cell types. The densest, in human lymphoblastoid cells, contains 4.9 billion contacts, achieving 1 kb resolution. We find that genomes are partitioned into contact domains (median length, 185 kb), which are associated with distinct patterns of histone marks and segregate into six subcompartments. We identify ∼10,000 loops. These loops frequently link promoters and enhancers, correlate with gene activation, and show conservation across cell types and species. Loop anchors typically occur at domain boundaries and bind CTCF. CTCF sites at loop anchors occur predominantly (>90%) in a convergent orientation, with the asymmetric motifs "facing" one another. The inactive X chromosome splits into two massive domains and contains large loops anchored at CTCF-binding repeats.

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      Affiliations
      [1 ] The Center for Genome Architecture, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Department of Computer Science, Department of Computational and Applied Mathematics, Rice University, Houston, TX 77005, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA.
      [2 ] The Center for Genome Architecture, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Department of Computer Science, Department of Computational and Applied Mathematics, Rice University, Houston, TX 77005, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
      [3 ] The Center for Genome Architecture, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Department of Computer Science, Department of Computational and Applied Mathematics, Rice University, Houston, TX 77005, USA.
      [4 ] The Center for Genome Architecture, Baylor College of Medicine, Houston, TX 77030, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA.
      [5 ] The Center for Genome Architecture, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Department of Computer Science, Department of Computational and Applied Mathematics, Rice University, Houston, TX 77005, USA; Department of Computer Science, Stanford University, Stanford, CA 94305, USA.
      [6 ] Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA; Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: lander@broadinstitute.org.
      [7 ] The Center for Genome Architecture, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Department of Computer Science, Department of Computational and Applied Mathematics, Rice University, Houston, TX 77005, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Center for Theoretical Biological Physics, Rice University, Houston, TX 77030, USA. Electronic address: erez@erez.com.
      Journal
      Cell
      Cell
      Elsevier BV
      1097-4172
      0092-8674
      Dec 18 2014
      : 159
      : 7
      25497547
      S0092-8674(14)01497-4
      10.1016/j.cell.2014.11.021

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