Epigenetic targeting of activation-induced cytidine deaminase

Qiao Wang, Thiago Oliveira, Mila Jankovic, Israel T. Silva, Ofir Hakim, Kaihui Yao, Anna Gazumyan, Christian T. Mayer, Rushad Pavri, Rafael Casellas, Michel C. Nussenzweig, Davide F. Robbiani

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


Activation-induced cytidine deaminase (AID) initiates class switch recombination (CSR) and somatic hypermutation (SHM) by deaminating cytosine residues in immunoglobulin genes (Igh, Igκ, and Igλ). At a lower frequency, AID also causes collateral DNA damage at non-Ig loci, including genes that are rearranged or mutated in B-cell lymphoma. Precisely how AID is recruited to these off-target sites is not entirely understood. To gain further insight into how AID selects its targets, we compared AID-mediated translocations in two different cell types, B cells and mouse embryonic fibroblasts (MEFs). AID targets a distinct set of hotspots in the two cell types. In both cases, hotspots are concentrated in highly transcribed but stalled genes. However, transcription alone is insufficient to recruit AID activity. Comparison of genes similarly transcribed in B cells and MEFs but targeted in only one of the two cell types reveals a common set of epigenetic features associated with AID recruitment in both cells. AID target genes are enriched in chromatin modifications associated with active enhancers (such as H3K27Ac) and marks of active transcription (such as H3K36me3) in both fibroblasts and B cells, indicating that these features are universal mediators of AID recruitment.

Original languageEnglish
Pages (from-to)18667-18672
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number52
StatePublished - 30 Dec 2014

Bibliographical note

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© 2014, National Academy of Sciences. All rights reserved.


  • Active enhancer
  • Chromosome translocation
  • Lymphoma
  • Mouse embryonic fibroblast
  • Transcription elongation


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