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...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 109; no. 7; pp. 2479 - 2484
Main Authors Kato, Lucia, Begum, Nasim A, Burroughs, A. Maxwell, Doi, Tomomitsu, Kawai, Jun, Daub, Carsten O, Kawaguchi, Takahisa, Matsuda, Fumihiko, Hayashizaki, Yoshihide, Honjo, Tasuku
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 14.02.2012
National Acad Sciences
Subjects
Activation-induced cytidine deaminase
AIDS
Biological Sciences
Biotin - metabolism
Cell lines
Cells
Chromatin
chromosome translocation
Chromosome translocations
Class switching
cytidine
Cytidine Deaminase - genetics
DNA
DNA cleavage
DNA damage
epigenetics
Genes
Genes, Immunoglobulin
Genetic loci
Genetic mutation
Genomes
Humans
immunoglobulin genes
Immunoglobulins
loci
Lymphocytes B
Methylation
Mutation
neoplasms
Polymerase Chain Reaction
Promoter regions
Recombination
repetitive sequences
Sequencing
somatic hypermutation
Transcription activation
Tumors
Online AccessGet full text
ISSN0027-8424
1091-6490
1091-6490
DOI10.1073/pnas.1120791109

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Summary: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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1Present address: Laboratory Animal Research Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Author contributions: L.K., T.D., and T.H. designed research; L.K., N.A.B., and A.M.B. performed research; T.K. and F.M. contributed new reagents/analytic tools; L.K., N.A.B., A.M.B., J.K., C.O.D., and Y.H. analyzed data; and L.K. and T.H. wrote the paper.
Contributed by Tasuku Honjo, December 28, 2011 (sent for review December 5, 2011)
ISSN:0027-8424
1091-6490
1091-6490
DOI:10.1073/pnas.1120791109