| RRC ID |
28589
|
| 著者 |
Tran TH, Nakata M, Suzuki K, Begum NA, Shinkura R, Fagarasan S, Honjo T, Nagaoka H.
|
| タイトル |
B cell-specific and stimulation-responsive enhancers derepress Aicda by overcoming the effects of silencers.
|
| ジャーナル |
Nat Immunol
|
| Abstract |
Activation-induced cytidine deaminase (AID) is essential for the generation of antibody memory but also targets oncogenes, among other genes. We investigated the transcriptional regulation of Aicda (which encodes AID) in class switch-inducible CH12F3-2 cells and found that Aicda regulation involved derepression by several layers of positive regulatory elements in addition to the 5' promoter region. The 5' upstream region contained functional motifs for the response to signaling by cytokines, the ligand for the costimulatory molecule CD40 or stimuli that activated the transcription factor NF-kappaB. The first intron contained functional binding elements for the ubiquitous silencers c-Myb and E2f and for the B cell-specific activator Pax5 and E-box-binding proteins. Our results show that Aicda is regulated by the balance between B cell-specific and stimulation-responsive elements and ubiquitous silencers.
|
| 巻・号 |
11(2)
|
| ページ |
148-54
|
| 公開日 |
2010-2-1
|
| DOI |
10.1038/ni.1829
|
| PII |
ni.1829
|
| PMID |
19966806
|
| MeSH |
Animals
B-Lymphocytes / immunology*
Cytidine Deaminase / genetics*
Cytidine Deaminase / immunology
Enhancer Elements, Genetic / genetics*
Enhancer Elements, Genetic / immunology
Gene Expression
Gene Expression Profiling
Gene Expression Regulation / immunology*
Genes, Immunoglobulin / genetics*
Genes, Immunoglobulin / immunology
Humans
Immunoglobulin Class Switching / genetics
Immunoglobulin Class Switching / immunology
Immunologic Memory / genetics
Immunologic Memory / immunology
Mice
Mutagenesis, Site-Directed
Oligonucleotide Array Sequence Analysis
Oncogenes / genetics
Oncogenes / immunology
Promoter Regions, Genetic / genetics
Promoter Regions, Genetic / immunology
Reverse Transcriptase Polymerase Chain Reaction
Silencer Elements, Transcriptional / genetics*
Silencer Elements, Transcriptional / immunology
Somatic Hypermutation, Immunoglobulin / genetics
Somatic Hypermutation, Immunoglobulin / immunology
|
| IF |
20.479
|
| 引用数 |
84
|
|
WOS 分野
|
IMMUNOLOGY
|
| リソース情報 |
| 遺伝子材料 |
pGL3-AID R3 (RDB07881)
pGL3-AID R1+R4 full (RDB07880)
pGL3-AID R2 + R4 Full length (RDB07854) |
