Epigenetic tethering of AID to the donor switch region during immunoglobulin class switch recombination.
| Title: | Epigenetic tethering of AID to the donor switch region during immunoglobulin class switch recombination. |
|---|---|
| Authors: | Jeevan-Raj BP; Institut de Génétique et de Biologie Moléculaire et Cellulaire, Institut National de Santé et de Recherche Médicale Unité 964/Centre National de Recherche Scientifique Unité Mixte de Recherche 7104, Université de Strasbourg, 67404 Illkirch, France.; Robert I; Heyer V; Page A; Wang JH; Cammas F; Alt FW; Losson R; Reina-San-Martin B |
| Source: | The Journal of experimental medicine [J Exp Med] 2011 Aug 01; Vol. 208 (8), pp. 1649-60. Date of Electronic Publication: 2011 Jul 11. |
| Publication Type: | Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Rockefeller University Press Country of Publication: United States NLM ID: 2985109R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1540-9538 (Electronic) Linking ISSN: 00221007 NLM ISO Abbreviation: J Exp Med Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: New York, NY : Rockefeller University Press |
| MeSH Terms: | B-Lymphocytes/*cytology ; Cytidine Deaminase/*immunology ; Epigenesis, Genetic/*immunology ; Immunoglobulin Class Switching/*immunology ; Immunoglobulin Switch Region/*immunology ; Nuclear Proteins/*immunology ; Repressor Proteins/*immunology; B-Lymphocytes/immunology ; Chromosomal Proteins, Non-Histone/metabolism ; DNA Primers/genetics ; Histones/metabolism ; Nuclear Proteins/genetics ; Nuclear Proteins/metabolism ; Repressor Proteins/genetics ; Repressor Proteins/metabolism ; Animals ; Blotting, Western ; Chromatin Immunoprecipitation ; Chromatography, Gel ; Chromobox Protein Homolog 5 ; DNA Mutational Analysis ; Flow Cytometry ; In Situ Hybridization, Fluorescence ; Mass Spectrometry ; Mice ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Tripartite Motif-Containing Protein 28 ; AICDA (Activation-Induced Cytidine Deaminase) |
| Abstract: | Immunoglobulin class switch recombination (CSR) is initiated by double-stranded DNA breaks (DSBs) in switch regions triggered by activation-induced cytidine deaminase (AID). Although CSR correlates with epigenetic modifications at the IgH locus, the relationship between these modifications and AID remains unknown. In this study, we show that during CSR, AID forms a complex with KAP1 (KRAB domain-associated protein 1) and HP1 (heterochromatin protein 1) that is tethered to the donor switch region (Sμ) bearing H3K9me3 (trimethylated histone H3 at lysine 9) in vivo. Furthermore, in vivo disruption of this complex results in impaired AID recruitment to Sμ, inefficient DSB formation, and a concomitant defect in CSR but not in somatic hypermutation. We propose that KAP1 and HP1 tether AID to H3K9me3 residues at the donor switch region, thus providing a mechanism linking AID to epigenetic modifications during CSR. |
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| Grant Information: | United States Howard Hughes Medical Institute |
| Substance Nomenclature: | 0 (Chromosomal Proteins, Non-Histone); 0 (DNA Primers); 0 (Histones); 0 (Nuclear Proteins); 0 (Repressor Proteins); 107283-02-3 (Chromobox Protein Homolog 5); EC 2.3.2.27 (Trim28 protein, mouse); EC 2.3.2.27 (Tripartite Motif-Containing Protein 28); EC 3.5.4.- (AICDA (Activation-Induced Cytidine Deaminase)); EC 3.5.4.5 (Cytidine Deaminase) |
| Entry Date(s): | Date Created: 20110713 Date Completed: 20111017 Latest Revision: 20250103 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC3149220 |
| DOI: | 10.1084/jem.20110118 |
| PMID: | 21746811 |
| Database: | MEDLINE |
Journal Article; Research Support, Non-U.S. Gov't