A 3D Map of the Human Genome at Kilobase Resolution Reveals Principles of Chromatin Looping

Cell. 2014 Dec 18;159(7):1665-80. doi: 10.1016/j.cell.2014.11.021. Epub 2014 Dec 11.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • CCCTC-Binding Factor
  • Cell Line
  • Cell Nucleus / chemistry
  • Cell Nucleus / genetics*
  • Chromatin / chemistry*
  • Gene Expression Regulation
  • Genome, Human*
  • Histone Code
  • Humans
  • Mice
  • Molecular Conformation
  • Regulatory Sequences, Nucleic Acid
  • Repressor Proteins / metabolism

Substances

  • CCCTC-Binding Factor
  • CTCF protein, human
  • Chromatin
  • Ctcf protein, mouse
  • Repressor Proteins

Associated data

  • GEO/GSE63525
  • dbGaP/PHS000640