The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Convergent Transcription at Intragenic Super-Enhancers Targets AID-Initiated Genomic Instability
Open accessAbstract
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 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.
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Self-citationAn atlas of active enhancers across human cell types and tissues
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RNA Exosome-Regulated Long Non-Coding RNA Transcription Controls Super-Enhancer Activity
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Self-citationRNA Binding to CBP Stimulates Histone Acetylation and Transcription
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Metadata
- Authors
- Meng, F.-L., Du, Z., Federation, A., Hu, J., Wang, Q., Kieffer-Kwon, K.-R., Meyers, R. M., Amor, C., Wasserman, C. R., Neuberg, D., Casellas, R., Nussenzweig, M. C., Bradner, J. E., Liu, X. S., & Alt, F. W.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2014-12
- Volume
- 159
- Issue
- 7
- Pages
- 1538-1548
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2093021355
- Cited by
- 253
- References
- 9
- FWCI
- 10.34
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Meng, F.-L., Du, Z., Federation, A., Hu, J., Wang, Q., Kieffer-Kwon, K.-R., Meyers, R. M., Amor, C., Wasserman, C. R., Neuberg, D., Casellas, R., Nussenzweig, M. C., Bradner, J. E., Liu, X. S., & Alt, F. W. (2014). Convergent Transcription at Intragenic Super-Enhancers Targets AID-Initiated Genomic Instability. Cell. https://doi.org/10.1016/j.cell.2014.11.014
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