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| Status |
Public on May 01, 2018 |
| Title |
The energetics and physiological impact of cohesin extrusion |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Other
Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
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| Summary |
Cohesin extrusion is thought to play a central role in establishing the architecture of mammalian genomes. However, extrusion has not been visualized in vivo, and thus, its functional impact and energetics are unknown. Using ultra-deep Hi-C, we show that loop domains form by a process that requires cohesin ATPases. Once formed, however, loops and compartments are maintained for hours without energy input. Strikingly, without ATP, we observe the emergence of hundreds of CTCF-independent loops that link regulatory DNA. We also identify architectural "stripes" where a loop anchor interacts with entire domains at high frequency. Stripes often tether super-enhancers to cognate promoters, and in B cells, they facilitate Igh transcription and recombination. Stripe anchors represent major hotspots for topoisomerase-mediated lesions, which promote chromosomal translocations and cancer. In plasmacytomas, stripes can deregulate Igh-translocated oncogenes. We propose that higher organisms have coopted cohesin extrusion to enhance transcription and recombination, with implications for tumor development.
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| Overall design |
ChIP-seq, ChIA-PET, insitu Hi-C, 4C, localHiC, ChromRNAseq, and/or RNAseq from mouse stem cells, activated B cells, CH12 cell line, and plasmacytomas
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| Contributor(s) |
Vian L, Pekowska A, Rao S, Kieffer-Kwon K, Jung S, Baranello L, Huang S, Dose M, Pruett N, Sanborn A, Canela A, Maman Y, Oksanen A, Resch W, Li X, Lee B, Kovalchuk A, Tang Z, Nelson S, Pierro MD, Cheng R, Machol I, Hilaire BG, Durand N, Shamim M, Stamenova E, Onuchic J, Ruan Y, Nussenzweig A, Levens D, Lieberman-Aiden E, Casellas R |
| Citation(s) |
29706548 |
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| Submission date |
Apr 24, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Seolkyoung Jung |
| Organization name |
NIH
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| Department |
NIAMS
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| Lab |
biodata mining and discovery section
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| Street address |
10 Center Dr
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| City |
bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (6)
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| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
| GPL21273 |
HiSeq X Ten (Mus musculus) |
| GPL21493 |
Illumina HiSeq 3000 (Mus musculus) |
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| Samples (352)
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| Relations |
| BioProject |
PRJNA384026 |
| SRA |
SRP105082 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE98119_7134_SAd_4C.bedGraph.gz |
443.8 Kb |
(ftp)(http) |
BEDGRAPH |
| GSE98119_7134_wt_4C.bedGraph.gz |
476.0 Kb |
(ftp)(http) |
BEDGRAPH |
| GSE98119_RAW.tar |
397.9 Gb |
(http)(custom) |
TAR (of BED, BW, HIC) |
| GSE98119_Series-level_HIC_readme.txt |
1.4 Kb |
(ftp)(http) |
TXT |
| GSE98119_Vian-2018-CH12_cells_CTCFZF9to11_mutant_30.hic |
12.8 Gb |
(ftp)(http) |
HIC |
| GSE98119_Vian-2018-CH12_cells_wt_30.hic |
15.2 Gb |
(ftp)(http) |
HIC |
| GSE98119_Vian-2018-activated_B_cells_24_hours_WT.hic |
3.4 Gb |
(ftp)(http) |
HIC |
| GSE98119_Vian-2018-activated_B_cells_24_hours_WT_30.hic |
3.1 Gb |
(ftp)(http) |
HIC |
| GSE98119_Vian-2018-activated_B_cells_24_hours_flavopiridol.hic |
14.9 Gb |
(ftp)(http) |
HIC |
| GSE98119_Vian-2018-activated_B_cells_24_hours_flavopiridol_30.hic |
14.0 Gb |
(ftp)(http) |
HIC |
| GSE98119_Vian-2018-activated_B_cells_24_hours_oligomycin_30.hic |
7.4 Gb |
(ftp)(http) |
HIC |
| GSE98119_Vian-2018-activated_B_cells_30_hours_HU_treated.hic |
1.4 Gb |
(ftp)(http) |
HIC |
| GSE98119_Vian-2018-activated_B_cells_30_hours_HU_treated_30.hic |
1.3 Gb |
(ftp)(http) |
HIC |
| GSE98119_Vian-2018-activated_B_cells_30_hours_WT.hic |
1.2 Gb |
(ftp)(http) |
HIC |
| GSE98119_Vian-2018-activated_B_cells_30_hours_WT_30.hic |
1.1 Gb |
(ftp)(http) |
HIC |
| GSE98119_aB72h_wt_PolII_ATPd_merged.bw |
313.6 Mb |
(ftp)(http) |
BW |
| GSE98119_aB72h_wt_PolII_merged.bw |
194.0 Mb |
(ftp)(http) |
BW |
| GSE98119_ch12_CTCFZF9to11_mRNA_merged.bw |
335.8 Mb |
(ftp)(http) |
BW |
| GSE98119_ch12_ZF9to11_CTCF_merged.bw |
46.5 Mb |
(ftp)(http) |
BW |
| GSE98119_ch12_ZF9to11_Rad21_merged.bw |
540.2 Mb |
(ftp)(http) |
BW |
| GSE98119_ch12_wt_CTCF_merged.bw |
369.1 Mb |
(ftp)(http) |
BW |
| GSE98119_ch12_wt_CTCF_peaks.bed.gz |
575.4 Kb |
(ftp)(http) |
BED |
| GSE98119_ch12a_SAd_merged.minus.bw |
218.9 Mb |
(ftp)(http) |
BW |
| GSE98119_ch12a_SAd_merged.plus.bw |
227.7 Mb |
(ftp)(http) |
BW |
| GSE98119_esc_wt_CTCF_merged.bw |
864.9 Mb |
(ftp)(http) |
BW |
| GSE98119_rBaB_CTCF_peaks.narrowPeak.gz |
1.6 Mb |
(ftp)(http) |
NARROWPEAK |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
| Processed data provided as supplementary file |
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