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Deep-sequencing identification of the genomic targets of the cytidine deaminase AID and its cofactor RPA in B lymphocytes
Open accessAbstract
The cytidine deaminase AID hypermutates immunoglobulin genes but can also target oncogenes, leading to tumorigenesis. The extent of AID's promiscuity and its predilection for immunoglobulin genes are unknown. We report here that AID interacted broadly with promoter-proximal sequences associated with stalled polymerases and chromatin-activating marks. In contrast, genomic occupancy of replication protein A (RPA), an AID cofactor, was restricted to immunoglobulin genes. The recruitment of RPA to the immunoglobulin loci was facilitated by phosphorylation of AID at Ser38 and Thr140. We propose that stalled polymerases recruit AID, thereby resulting in low frequencies of hypermutation across the B cell genome. Efficient hypermutation and switch recombination required AID phosphorylation and correlated with recruitment of RPA. Our findings provide a rationale for the oncogenic role of AID in B cell malignancy.
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High-Resolution Profiling of Histone Methylations in the Human Genome
Barski, A., Cuddapah, S., Cui, K., Roh, T.-Y., Schones, D. E., Wang, Z., Wei, G., Chepelev, I., & Zhao, K. (2007) · Cell · doi:10.1016/j.cell.2007.05.009 · Cited by 6,845
Genome-wide maps of chromatin state in pluripotent and lineage-committed cells
Mikkelsen, T. S., Ku, M., Jaffe, D. B., Issac, B., Lieberman, E., Giannoukos, G., Alvarez, P., Brockman, W., Kim, T.-K., Koche, R. P., et al. (2007) · Nature · doi:10.1038/nature06008 · Cited by 4,129
Defining mechanisms that regulate RNA polymerase II transcription in vivo
Fuda, N. J., Ardehali, M. B., & Lis, J. T. (2009) · Nature · doi:10.1038/nature08449 · Cited by 576
Cited by
Victora, G. D., & Nussenzweig, M. C. (2012) · Annual Review of Immunology · doi:10.1146/annurev-immunol-020711-075032 · Cited by 1,878
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Nie, Z., Hu, G., Wei, G., Cui, K., Yamane, A., Resch, W., Wang, R., Green, D. R., Tessarollo, L., Casellas, R., et al. (2012) · Cell · doi:10.1016/j.cell.2012.08.033 · Cited by 1,075
Self-citationR-Loop Formation Is a Distinctive Characteristic of Unmethylated Human CpG Island Promoters
Ginno, P. A., Lott, P. L., Christensen, H. C., Korf, I., & Chédin, F. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.01.017 · Cited by 910
Non-coding recurrent mutations in chronic lymphocytic leukaemia
Puente, X. S., Beà, S., Valdés-Mas, R., Villamor, N., Gutiérrez-Abril, J., Martín-Subero, J. I., Munar, M., Rubio-Pérez, C., Jares, P., Aymerich, M., et al. (2015) · Nature · doi:10.1038/nature14666 · Cited by 829
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Metadata
- Authors
- Yamane, A., Resch, W., Kuo, N., Kuchen, S., Li, Z., Sun, H.-W., Robbiani, D. F., McBride, K., Nussenzweig, M. C., & Casellas, R.
- Venue
- Nature Immunology
- Published
- 2010-11-28
- Volume
- 12
- Issue
- 1
- Pages
- 62-69
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W2170629396
- Cited by
- 290
- References
- 3
- FWCI
- 14.06
- Type
- journal article
- Language
- en
- Open access
- green
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- Yamane, A., Resch, W., Kuo, N., Kuchen, S., Li, Z., Sun, H.-W., Robbiani, D. F., McBride, K., Nussenzweig, M. C., & Casellas, R. (2011). Deep-sequencing identification of the genomic targets of the cytidine deaminase AID and its cofactor RPA in B lymphocytes. Nature Immunology. https://doi.org/10.1038/ni.1964
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