Journal
CELL
Volume 159, Issue 7, Pages 1665-1680Publisher
CELL PRESS
DOI: 10.1016/j.cell.2014.11.021
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Funding
- NSF Graduate Research Fellowship [DGE0946799, DGE1144152]
- NIH New Innovator Award [OD008540-01]
- NSF Physics Frontier Center (Center for Theoretical Biological Physics) [PHY-1427654]
- NHGRI CEGS [HG006193]
- NVIDIA
- IBM
- CPRIT Scholar Award [R1304]
- McNair Medical Institute Scholar Award
- President's Early Career Award in Science and Engineering
- NHGRI grant [HG003067]
- Center for Genome Architecture
- Division Of Physics
- Direct For Mathematical & Physical Scien [1427654] Funding Source: National Science Foundation
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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 similar to 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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