| HoxC4 binds to the promoter of the cytidine deaminase AID gene to induce AID expression, class-switch DNA recombination and somatic hypermutation. | |
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MedLine Citation:
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PMID: 19363484 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The cytidine deaminase AID (encoded by Aicda in mice and AICDA in humans) is critical for immunoglobulin class-switch recombination (CSR) and somatic hypermutation (SHM). Here we show that AID expression was induced by the HoxC4 homeodomain transcription factor, which bound to a highly conserved HoxC4-Oct site in the Aicda or AICDA promoter. This site functioned in synergy with a conserved binding site for the transcription factors Sp1, Sp3 and NF-kappaB. HoxC4 was 'preferentially' expressed in germinal center B cells and was upregulated by engagement of CD40 by CD154, as well as by lipopolysaccharide and interleukin 4. HoxC4 deficiency resulted in impaired CSR and SHM because of lower AID expression and not some other putative HoxC4-dependent activity. Enforced expression of AID in Hoxc4(-/-) B cells fully restored CSR. Thus, HoxC4 directly activates the Aicda promoter, thereby inducing AID expression, CSR and SHM. |
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Authors:
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Seok-Rae Park; Hong Zan; Zsuzsanna Pal; Jinsong Zhang; Ahmed Al-Qahtani; Egest J Pone; Zhenming Xu; Thach Mai; Paolo Casali |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2009-04-12 |
Journal Detail:
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Title: Nature immunology Volume: 10 ISSN: 1529-2916 ISO Abbreviation: Nat. Immunol. Publication Date: 2009 May |
Date Detail:
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Created Date: 2009-04-21 Completed Date: 2009-06-05 Revised Date: 2010-12-03 |
Medline Journal Info:
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Nlm Unique ID: 100941354 Medline TA: Nat Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 540-50 Citation Subset: IM |
Affiliation:
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Institute for Immunology, School of Medicine and School of Biological Sciences, University of California, Irvine, California, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals B-Lymphocytes / immunology* Base Sequence Conserved Sequence Cytidine Deaminase / genetics*, metabolism Electrophoretic Mobility Shift Assay Flow Cytometry Gene Expression Regulation / immunology* Germinal Center / cytology, immunology Homeodomain Proteins / genetics, immunology*, metabolism Humans Immunoglobulin Class Switching / immunology* Immunoprecipitation Mice Mice, Inbred C57BL Mice, Transgenic Peyer's Patches / cytology, immunology Promoter Regions, Genetic / genetics Recombination, Genetic Reverse Transcriptase Polymerase Chain Reaction Somatic Hypermutation, Immunoglobulin / immunology* Spleen / cytology, immunology T-Lymphocytes |
| Grant Support | |
ID/Acronym/Agency:
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AI 045011/AI/NIAID NIH HHS; AI 060573/AI/NIAID NIH HHS; AI 079705/AI/NIAID NIH HHS; R01 AI045011-06A1/AI/NIAID NIH HHS; R01 AI045011-07/AI/NIAID NIH HHS; R01 AI045011-08/AI/NIAID NIH HHS; R01 AI045011-10/AI/NIAID NIH HHS; R01 AI079705-02/AI/NIAID NIH HHS; R56 AI079705-01/AI/NIAID NIH HHS; T32 AI060573-01A1/AI/NIAID NIH HHS; T32 AI060573-02/AI/NIAID NIH HHS; T32 AI060573-03/AI/NIAID NIH HHS; T32 AI060573-04/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Homeodomain Proteins; 0/Hoxc4 protein, mouse; EC 3.5.4.-/AICDA (activation-induced cytidine deaminase); EC 3.5.4.5/Cytidine Deaminase |
| Comments/Corrections | |
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