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Status |
Public on May 31, 2018 |
Title |
Distinct roles of cohesin-SA1 and cohesin-SA2 in 3D chromosome organization |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing Genome binding/occupancy profiling by high throughput sequencing Other
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Summary |
In addition to mediating sister chromatid cohesion, cohesin plays a central role in DNA looping and segmentation of the genome into contact domains (TADs). Two variant cohesin complexes that contain either STAG/SA1 or SA2 are present in all cell types. Here we addressed their specific contribution to genome architecture in non-transformed human cells. We found that cohesin-SA1 drives stacking of cohesin rings at CTCF-bound sites and thereby contributes to the stabilization and preservation of TAD boundaries. In contrast, a more dynamic cohesin-SA2 promotes cell type-specific contacts between enhancers and promoters within TADs independently of CTCF. SA2 loss, a condition frequently observed in cancer cells, results in increased intra-TAD interactions, likely altering the expression of key cell identity genes.
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Overall design |
ChIP-seq for cohesin subunits SMC1, SA1 and SA2 was performed in 3 different cell lines (MCF10A, HMEC, HCAEC) and peak calling was done against the input sample from the corresponding cell line. RNA-seq was performed in triplicates in MCF10A cells control depleated from SA1, SA2 or CTCF by means of Dharmacon SMART pool siRNAs. HiC-seq was performed in two replicates in MCF10A cells control and depleated from SA1 and SA2 by means of Dharmacon SMART pool siRNAs. 4C-seq was performed in MCF10A cells control and depleated from SA2 or CTCF.
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Contributor(s) |
Kojic A, Cuadrado A, Gimenez D, De Koninck M, Rodríguez-Corsino M, Gómez-López G, Le Dily F, Marti-Renom MA, Losada A |
Citation(s) |
29867216 |
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Submission date |
Jul 26, 2017 |
Last update date |
Jul 25, 2021 |
Contact name |
Ana Losada |
E-mail(s) |
[email protected]
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Phone |
+34 - 917 328 000
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Organization name |
Centro Nacional de Investigaciones Oncológicas (CNIO)
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Department |
Molecular Oncology Programme
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Lab |
Chromosome Dynamics Group
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Street address |
C/ Melchor Fernández Almagro, 3.
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City |
Madrid |
State/province |
Madrid |
ZIP/Postal code |
28029 |
Country |
Spain |
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Platforms (3) |
GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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Samples (45)
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Relations |
BioProject |
PRJNA395931 |
SRA |
SRP113633 |