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B cell–specific and stimulation-responsive enhancers derepress Aicda by overcoming the effects of silencers
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Description
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-κB. 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.
Journal
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- Nature Immunology
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Nature Immunology 11 (2), 148-154, 2009-12-06
Nature Publishing Group
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Keywords
- B-Lymphocytes
- Genes, Immunoglobulin
- Reverse Transcriptase Polymerase Chain Reaction
- Gene Expression Profiling
- Gene Expression
- Oncogenes
- Immunoglobulin Class Switching
- Mice
- Enhancer Elements, Genetic
- Gene Expression Regulation
- Cytidine Deaminase
- Mutagenesis, Site-Directed
- Silencer Elements, Transcriptional
- Animals
- Humans
- Somatic Hypermutation, Immunoglobulin
- Promoter Regions, Genetic
- Immunologic Memory
- Oligonucleotide Array Sequence Analysis
Details 詳細情報について
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- CRID
- 1050001202111018112
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- NII Article ID
- 120001741673
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- ISSN
- 15292908
- 15292916
- http://id.crossref.org/issn/15292908
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- DOI
- 10.1038/ni.1829
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- HANDLE
- 2433/88755
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- PubMed
- 20084065
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- Text Lang
- en
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- Article Type
- journal article
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- Data Source
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- IRDB
- Crossref
- CiNii Articles
- OpenAIRE