Molecular Cell
Volume 47, Issue 6, 28 September 2012, Pages 873-885
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Article
Close Proximity to Igh Is a Contributing Factor to AID-Mediated Translocations

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Summary

Class switch recombination (CSR) has the potential to generate genomic instability in B cells as activation-induced cytidine deaminase (AID), which mediates this process, is known to target many sites outside Igh. Nonetheless we do not fully understand what factors influence AID targeting genome-wide. Given that errors in CSR can lead to dangerous, oncogenic chromosomal translocations it is important to identify the elements that determine which genes are at risk of being “hit” and could be involved in aberrant rearrangements. Here we have investigated the influence of nuclear organization in determining “off-target” activity and the choice of fusion partners. Our studies indicate that the vast majority of known AID-mediated Igh translocation partners are found in chromosomal domains that contact this locus during class switching. Further, these interaction domains can be used to identify other genes that are hit by AID.

Highlights

► AID target hotspots are located in chromosomal domains that interact with IghIgh interacting domains can be used to identify new targets of AID ► The method of analysis will impact on the conclusions of a 4C-seq study

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These authors contributed equally to this work