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B Cell Super-Enhancers and Regulatory Clusters Recruit AID Tumorigenic Activity

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Qian, Jason, Wang, Qiao, Dose, Marei, Pruett, Nathanael, Kieffer-Kwon, Kyong-Rim, Resch, Wolfgang, Liang, Genqing, Tang, Zhonghui, Mathé, Ewy, Benner, Christopher, Dubois, Wendy, Nelson, Steevenson, Vian, Laura, Oliveira, Thiago Y., Jankovic, Mila, Hakim, Ofir, Gazumyan, Anna, Pavri, Rushad, Awasthi, Parirokh, Song, Bin, Liu, Geng, Chen, Longyun, Zhu, Shida, Feigenbaum, Lionel, Staudt, Louis, Murre, Cornelis, Ruan, Yijun, Robbiani, Davide F., Pan-Hammarström, Qiang, Nussenzweig, Michel C., Casellas, Rafael·2014·Cell
DOI 10.1016/j.cell.2014.11.013
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Abstract

SUMMARY The antibody gene mutator activation-induced cytidine deaminase (AID) promiscuously damages oncogenes, leading to chromosomal translocations and tumorigenesis. Why nonimmunoglobulin loci are susceptible to AID activity is unknown. Here, we study AID-mediated lesions in the context of nuclear architecture and the B cell regulome. We show that AID targets are not randomly distributed across the genome but are predominantly grouped within super-enhancers and regulatory clusters. Unexpectedly, in these domains, AID deaminates active promoters and eRNA+ enhancers interconnected in some instances over megabases of linear chromatin. Using genome editing, we demonstrate that 3D-linked targets cooperate to recruit AID-mediated breaks. Furthermore, a comparison of hypermutation in mouse B cells, AID-induced kataegis in human lymphomas, and translocations in MEFs reveals that AID damages different genes in different cell types. Yet, in all cases, the targets are predominantly associated with topological complex, highly transcribed super-enhancers, demonstrating that these compartments are key mediators of AID recruitment.

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Metadata

Authors
Qian, J., Wang, Q., Dose, M., Pruett, N., Kieffer-Kwon, K.-R., Resch, W., Liang, G., Tang, Z., Mathé, E., Benner, C., Dubois, W., Nelson, S., Vian, L., Oliveira, T. Y., Jankovic, M., Hakim, O., Gazumyan, A., Pavri, R., Awasthi, P., Song, B., Liu, G., Chen, L., Zhu, S., Feigenbaum, L., Staudt, L., Murre, C., Ruan, Y., Robbiani, D. F., Pan-Hammarström, Q., Nussenzweig, M. C., & Casellas, R.
Venue
Cell
Publisher
Elsevier BV
Published
2014-12
Volume
159
Issue
7
Pages
1524-1537
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2014.11.013
OpenAlex
W2086425717
Cited by
267
References
13
FWCI
12.29
Type
journal article
Language
en
Open access
bronze
Licence

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CoChat. (2026). Citation check: B Cell Super-Enhancers and Regulatory Clusters Recruit AID Tumorigenic Activity. https://app.cochat.ai/papers/10.1016/j.cell.2014.11.013
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Qian, J., Wang, Q., Dose, M., Pruett, N., Kieffer-Kwon, K.-R., Resch, W., Liang, G., Tang, Z., Mathé, E., Benner, C., Dubois, W., Nelson, S., Vian, L., Oliveira, T. Y., Jankovic, M., Hakim, O., Gazumyan, A., Pavri, R., Awasthi, P., . . . Casellas, R. (2014). B Cell Super-Enhancers and Regulatory Clusters Recruit AID Tumorigenic Activity. Cell. https://doi.org/10.1016/j.cell.2014.11.013

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