Open AccessNonimmunoglobulin target loci of activation-induced cytidine deaminase (AID) share unique features with immunoglobulin genes
Author(s) -
Lucia M. Kato,
Nasim A. Begum,
A. Maxwell Burroughs,
Tomomitsu Doi,
Jun Kawai,
Carsten O. Daub,
Takahisa Kawaguchi,
Fumihiko Matsuda,
Yoshihide Hayashizaki,
Tasuku Honjo
Publication year - 2012
Publication title -
proceedings of the national academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.1120791109
Subject(s) - cytidine deaminase , somatic hypermutation , activation induced (cytidine) deaminase , biology , gene , genetics , immunoglobulin class switching , locus (genetics) , genome , chromosomal translocation , chromatin , microbiology and biotechnology , antibody , b cell
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.
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