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

被引:4854
作者
Rao, Suhas S. P. [1 ,2 ,3 ,4 ]
Huntley, Miriam H. [1 ,2 ,3 ,4 ,5 ]
Durand, Neva C. [1 ,2 ,3 ,4 ]
Stamenova, Elena K. [1 ,2 ,3 ,4 ]
Bochkov, Ivan D. [1 ,2 ,3 ]
Robinson, James T. [1 ,4 ]
Sanborn, Adrian L. [1 ,2 ,3 ,6 ]
Machol, Ido [1 ,2 ,3 ]
Omer, Arina D. [1 ,2 ,3 ]
Lander, Eric S. [4 ,7 ,8 ]
Aiden, Erez Lieberman [1 ,2 ,3 ,4 ,9 ]
机构
[1] Baylor Coll Med, Ctr Genome Architecture, Houston, TX 77030 USA
[2] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA
[3] Rice Univ, Dept Computat & Appl Math, Dept Comp Sci, Houston, TX 77005 USA
[4] Broad Inst MIT & Harvard, Cambridge, MA 02139 USA
[5] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA
[6] Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA
[7] MIT, Dept Biol, Cambridge, MA 02139 USA
[8] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA
[9] Rice Univ, Ctr Theoret Biol Phys, Houston, TX 77030 USA
基金
美国国家科学基金会;
关键词
LONG-RANGE INTERACTION; SUPERCOILED LOOPS; GENE-REGULATION; CTCF; CHROMOSOME; TRANSCRIPTION; ORGANIZATION; CONFORMATION; LANDSCAPE; DOMAINS;
D O I
10.1016/j.cell.2014.11.021
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:1665 / 1680
页数:16
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