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| Status |
Public on Dec 04, 2019 |
| Title |
Topologically Associated Domains Delineate Susceptibility to Somatic Hypermutation |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
Other
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| Summary |
Somatic hypermutation (SHM) introduces point mutations into immunoglobulin (Ig) genes of activated B cells to support the process of antibody affinity maturation but also causes "off-target" mutations in other parts of the genome. We have used sensitive lentiviral SHM reporter vectors and a mutationally active human B cell line to identify dozens of regions of the genome that are intrinsically susceptible to SHM ("hot" regions) and many hundreds of regions that are resistant to SHM ("cold" regions). Hot and cold regions are frequently contained within topologically associated domains (TADs). Comparison of hot and cold TADs reveals that while overall levels of transcription are equal, hot TADs are enriched for NIPBL (a component of the cohesin loader), super enhancers, markers of paused/stalled RNA polymerase 2, and multiple transcription factors implicated in B cell development and targeting of SHM. We demonstrate that at least some hot TADs contain enhancer elements that possess SHM targeting activity and that insertion of a strong Ig SHM-targeting element into a cold TAD renders it hot. Our findings lead to a model for SHM susceptibility involving the cooperative action of cis-acting SHM targeting elements and the dynamic and architectural properties of TADs.
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| Overall design |
27 samples of ChIP-seq profiles in Ramos cell line including the Input and H3 control samples. 30 samples of HTISA libraries showing GFP7 integration site profiles in Ramos cell line. 2 samples of ATAC-seq profile in Ramos cell line. 4 samples of Hi-C profile in Ramos cell line.
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| Contributor(s) |
Senigl F, Maman Y, Dinesh RK, Alinikula J, Seth RB, Pecnova L, Omer AD, Rao SS, Weisz D, Buerstedde J, Aiden EL, Casellas R, Hejnar J, Schatz DG |
| Citation(s) |
31851922 |
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| Submission date |
Nov 01, 2019 |
| Last update date |
Nov 29, 2022 |
| Contact name |
Yaakov Maman |
| Organization name |
Bar-Ilan University
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| Department |
Azrieli Faculty of Medicine
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| Lab |
Genome Instability & Cancer
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| Street address |
Henrietta Szold 8
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| City |
Safed |
| ZIP/Postal code |
1311502 |
| Country |
Israel |
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| Platforms (2) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (69)
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| Relations |
| BioProject |
PRJNA587064 |
| SRA |
SRP227918 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE139810_RAW.tar |
21.6 Gb |
(http)(custom) |
TAR (of BW, HIC, WIG) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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