| Literature DB >> 25483776 |
Fei-Long Meng1, Zhou Du2, Alexander Federation3, Jiazhi Hu1, Qiao Wang4, Kyong-Rim Kieffer-Kwon5, Robin M Meyers1, Corina Amor1, Caitlyn R Wasserman1, Donna Neuberg6, Rafael Casellas5, Michel C Nussenzweig4, James E Bradner7, X Shirley Liu6, Frederick W Alt8.
Abstract
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.Entities:
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Year: 2014 PMID： 25483776 PMCID： PMC4322776 DOI： 10.1016/j.cell.2014.11.014
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582