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| Status |
Public on Dec 04, 2014 |
| Title |
Convergent Sense/Antisense Transcription At Intragenic Super-Enhancers Targets AID-initiated Genomic Instability |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Other
|
| Summary |
Activation-induced cytidine deaminase (AID) initiates both somatic hypermutation (SHM) for antibody affinity maturation and DNA breakage for antibody class switch recombination (CSR) via transcription-dependent cytidine deamination of single stranded DNA targets. While largely specific for immunglobulin genes, AID also acts on a limited set of off-targets, generating oncogenic translocations and mutations that contribute to B cell lymphoma. How AID is recruited to off-targets has been a long-standing mystery. Based on deep GRO-Seq studies of mouse and human B lineage cells activated for CSR or SHM, we report that most robust AID off-target translocations occur within highly focal regions of target genes in which sense and antisense transcription converge. Moreover, we found that such AID-targeting "convergent" transcription arises from antisense transcription that emanates from Super-Enhancers within sense transcribed gene bodies. Our findings provide a mechanistic explanation for AID off-targeting to a small subset of mostly lineage-specific genes in activated B cells.
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| |
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| Overall design |
We performed GRO-Seq and H3K27Ac ChIP-Seq with different B lineage cell types and MEF cells to find the signatures associated with AID targeting.
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| |
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| Contributor(s) |
Meng F, Alt FW |
| Citation(s) |
25483776 |
| Submission date |
Oct 14, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Feilong Meng |
| E-mail(s) |
feilong.meng@childrens.harvard.edu
|
| Organization name |
Boston Children's Hospital
|
| Department |
PCMM
|
| Lab |
Fredrick W Alt Lab
|
| Street address |
300 Longwood Ave
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
| |
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| Platforms (3) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
|
| Samples (9)
|
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| Relations |
| BioProject |
PRJNA263795 |
| SRA |
SRP048895 |
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