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Series GSE74072 Query DataSets for GSE74072
Status Public on Oct 23, 2015
Title Chromatin extrusion explains key features of loop and domain formation in wild-type and engineered genomes
Organism Homo sapiens
Experiment type Other
Summary We recently used in situ Hi-C to create kilobase-resolution 3D maps of mammalian genomes. Here, we combine these with new Hi-C, microscopy, and genome-editing experiments to study the physical structure of chromatin fibers, domains, and loops. We find that the observed contact domains are inconsistent with the equilibrium state for an ordinary condensed polymer. Combining Hi-C data and novel mathematical theorems, we show that contact domains are also not consistent with a fractal globule. Instead, we use physical simulations to study two models of genome folding. In one, intermonomer attraction during polymer condensation leads to formation of an anisotropic "tension globule." In the other, CTCF and cohesin act together to extrude loops during interphase. Both models are consistent with the observed contact domains and with the observation that contact domains tend to form inside loops. However, the extrusion model explains a far wider array of observations, such as why loops tend not to overlap and why the CTCF-binding motifs at pairs of loop anchors lie in the convergent orientation. Finally, we perform 13 genome-editing experiments examining the effect of altering CTCF-binding sites on chromatin folding. The convergent rule correctly predicts the affected loop in every case. Moreover, the extrusion model accurately predicts in silico the 3D maps resulting from each experiment using only the location of CTCF-binding sites in the WT. Thus, we show that it is possible to disrupt, restore, and move loops and domains using targeted mutations as small as a single base pair.
 
Overall design in situ Hi-C and HYbrid Capture Hi-C (Hi-C2) were used to probe the three-dimensional structure of the genome in two different human cell types before and after genome editing.
 
Contributor(s) Sanborn A, Rao S, Aiden EL
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Submission date Oct 15, 2015
Last update date Mar 14, 2019
Contact name Suhas Rao
E-mail suhasrao@post.harvard.edu
Organization name Baylor College of Medicine
Department Molecular and Human Genetics
Lab The Center for Genome Architecture
Street address 1 Baylor Plaza
City Houston
State/province TX
ZIP/Postal code 77030
Country USA
 
Platforms (4)
GPL15520 Illumina MiSeq (Homo sapiens)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (74)
GSM1909121 SanbornRao-2015-HIC001
GSM1909122 SanbornRao-2015-HIC002
GSM1909123 SanbornRao-2015-HIC003
Relations
BioProject PRJNA299007
SRA SRP064914

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE74072_Hap1_Arrowhead_domainlist.txt.gz 111.0 Kb (ftp)(http) TXT
GSE74072_Hap1_HiCCUPS_looplist.txt.gz 500.7 Kb (ftp)(http) TXT
Raw data are available in SRA
Processed data is available on Series record

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