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Proc Natl Acad Sci U S A. 2012 Feb 14;109(7):2479-84. doi: 10.1073/pnas.1120791109. Epub 2012 Jan 30.

Nonimmunoglobulin target loci of activation-induced cytidine deaminase (AID) share unique features with immunoglobulin genes.

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1
Department of Immunology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.

Abstract

Activation-induced cytidine deaminase (AID) is required for both somatic hypermutation and class-switch recombination in activated B cells. AID is also known to target nonimmunoglobulin genes and introduce mutations or chromosomal translocations, eventually causing tumors. To identify as-yet-unknown AID targets, we screened early AID-induced DNA breaks by using two independent genome-wide approaches. Along with known AID targets, this screen identified a set of unique genes (SNHG3, MALAT1, BCL7A, and CUX1) and confirmed that these loci accumulated mutations as frequently as Ig locus after AID activation. Moreover, these genes share three important characteristics with the Ig gene: translocations in tumors, repetitive sequences, and the epigenetic modification of chromatin by H3K4 trimethylation in the vicinity of cleavage sites.

PMID:
22308462
PMCID:
PMC3289292
DOI:
10.1073/pnas.1120791109
[Indexed for MEDLINE]
Free PMC Article
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