Nonimmunoglobulin target loci of activation-induced cytidine deaminase (AID) share unique features with immunoglobulin genes.
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.
Department of Immunology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
Lucia
L
Kato
Nasim A
NA
Begum
A Maxwell
AM
Burroughs
Tomomitsu
T
Doi
Jun
J
Kawai
Carsten O
CO
Daub
Takahisa
T
Kawaguchi
Fumihiko
F
Matsuda
Yoshihide
Y
Hayashizaki
Tasuku
T
Honjo
D001710:Biotin / Q000378:metabolism; D003564:Cytidine Deaminase / Q000235:genetics*; D005803:Genes, Immunoglobulin; D006801:Humans; D009154:Mutation; D016133:Polymerase Chain Reaction; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D001710:Biotin; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase