| First Author | Meng FL | Year | 2014 |
| Journal | Cell | Volume | 159 |
| Issue | 7 | Pages | 1538-48 |
| PubMed ID | 25483776 | Mgi Jnum | J:357142 |
| Mgi Id | MGI:6851764 | Doi | 10.1016/j.cell.2014.11.014 |
| Citation | Meng FL, et al. (2014) Convergent transcription at intragenic super-enhancers targets AID-initiated genomic instability. Cell 159(7):1538-48 |
| abstractText | 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. Though largely specific for immunoglobulin 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 an explanation for AID off-targeting to a small subset of mostly lineage-specific genes in activated B cells. |
