期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 109, 期 7, 页码 2479-2484出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1120791109
关键词
deep sequencing; end labeling by biotin oligonucleotide; microarray
资金
- RIKEN Omics Science Center from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan
- MEXT of Japan [17002015]
- Grants-in-Aid for Scientific Research [17002015] Funding Source: KAKEN
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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