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

被引：59

作者：

Kato, Lucia ^{[1
]}

Begum, Nasim A. ^{[1
]}

Burroughs, A. Maxwell ^{[3
]}

Doi, Tomomitsu ^{[1
]}

Kawai, Jun ^{[3
]}

Daub, Carsten O. ^{[3
]}

Kawaguchi, Takahisa ^{[2
]}

Matsuda, Fumihiko ^{[2
]}

Hayashizaki, Yoshihide ^{[3
]}

Honjo, Tasuku ^{[1
]}

机构：

[1] Kyoto Univ, Dept Immunol & Genom Med, Grad Sch Med, Kyoto 6068501, Japan

[2] Kyoto Univ, Ctr Genom Med, Grad Sch Med, Kyoto 6068501, Japan

[3] RIKEN Yokohama Inst, RIKEN Om Sci Ctr OSC, Yokohama, Kanagawa 2300045, Japan

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2012年 / 109卷 / 07期

关键词：

deep sequencing; end labeling by biotin oligonucleotide; microarray; CLASS-SWITCH RECOMBINATION; SOMATIC HYPERMUTATION; B-CELLS; TOPOISOMERASE; DNA CLEAVAGE; CONSTITUTIVE EXPRESSION; TRANSCRIPTION; MUTATION; REGION; CHROMATIN;

D O I：

10.1073/pnas.1120791109

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：2479 / 2484

页数：6

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