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| Status |
Public on Jan 21, 2011 |
| Title |
Activation-induced cytidine deaminase induces reproducible DNA breaks at many non-Ig loci in activated B cells |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by genome tiling array
|
| Summary |
After immunization or infection, activation-induced cytidine deaminase (AID) initiates diversification of immunoglobulin (Ig) genes in B cells, introducing mutations within the antigen binding V regions (somatic hypermutation, SHM) and double-strand DNA breaks (DSBs) into switch (S) regions, leading to antibody class switch recombination (CSR). Using a candidate approach, AID has been shown to initiate mutations at numerous non-Ig genes in B cells in Peyer’s patches. However, it is not known if during B cell activation, AID also induces DNA breaks at genes other than IgH genes, which would lead to genomic instability and malignancy. Using a non-biased genome-wide approach, we have identified hundreds of reproducible AID-dependent DSBs in mouse splenic B cells shortly after induction of CSR in culture. Most interestingly, AID induces DSBs at sites syntenic with sites of translocations, deletions, and amplifications found in human B cell lymphomas, including within the oncogene B cell lymphoma11a (bcl11a)/evi9. The AID-dependent DSBs are not restricted to transcribed regions, and they frequently occur within repeated sequence elements, including CA and non-CA repeats, and SINEs.
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| Overall design |
Comparison of Nbs1 binding sites in wild-type vs. aid-/- splenic B cells induced to undergo CSR; aid-dependent Nbs1 sites correlated with gene transcription (RNA Pol2).
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| Contributor(s) |
Staszewski O, Baker RE, Ucher AJ, Martier R, Stavnezer J, Guikema JE |
| Citation(s) |
21255732 |
| |
| Submission date |
Oct 20, 2010 |
| Last update date |
Mar 22, 2012 |
| Contact name |
Richard E Baker |
| E-mail(s) |
richard.baker@umassmed.edu
|
| Phone |
508-856-6046
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| Organization name |
University of Massachusetts Medical School
|
| Department |
Microbiology & Physiological Systems
|
| Street address |
55 Lake Avenue North
|
| City |
Worcester |
| State/province |
MA |
| ZIP/Postal code |
01655 |
| Country |
USA |
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| Platforms (10)
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| GPL11075 |
Mouse ChIP 2.1M WG-T Set-10 (1 of 10) |
| GPL11090 |
Mouse ChIP 2.1M WG-T Set-10 (2 of 10) |
| GPL11091 |
Mouse ChIP 2.1M WG-T Set-10 (3 of 10) |
| GPL11092 |
Mouse ChIP 2.1M WG-T Set-10 (4 of 10) |
| GPL11100 |
Mouse ChIP 2.1M WG-T Set-10 (5 of 10) |
| GPL11101 |
Mouse ChIP 2.1M WG-T Set-10 (6 of 10) |
| GPL11103 |
Mouse ChIP 2.1M WG-T Set-10 (7 of 10) |
| GPL11104 |
Mouse ChIP 2.1M WG-T Set-10 (8 of 10) |
| GPL11105 |
Mouse ChIP 2.1M WG-T Set-10 (9 of 10) |
| GPL11106 |
Mouse ChIP 2.1M WG-T Set-10 (10 of 10) |
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| Samples (60)
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| Relations |
| BioProject |
PRJNA132039 |
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