RRC ID 28589
Author Tran TH, Nakata M, Suzuki K, Begum NA, Shinkura R, Fagarasan S, Honjo T, Nagaoka H.
Title B cell-specific and stimulation-responsive enhancers derepress Aicda by overcoming the effects of silencers.
Journal 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.
Volume 11(2)
Pages 148-54
Published 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
Times Cited 84
DNA material pGL3-AID R3 (RDB07881) pGL3-AID R1+R4 full (RDB07880) pGL3-AID R2 + R4 Full length (RDB07854)