Epigenetic tethering of AID to the donor switch region during immunoglobulin class switch recombination
Copyright policy )Epigenetic tethering of AID to the donor switch region during immunoglobulin class switch recombination
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.
570, Chromatin Immunoprecipitation, Chromosomal Proteins, Non-Histone, Blotting, Western, DNA Mutational Analysis, 610, Article, Mass Spectrometry, Epigenesis, Genetic, Histones, Mice, Cytidine Deaminase, Animals, In Situ Hybridization, Fluorescence, DNA Primers, B-Lymphocytes, Flow Cytometry, Immunoglobulin Class Switching, Mice, Mutant Strains, Immunoglobulin Switch Region, Mice, Inbred C57BL, Chromobox Protein Homolog 5, Chromatography, Gel
570, Chromatin Immunoprecipitation, Chromosomal Proteins, Non-Histone, Blotting, Western, DNA Mutational Analysis, 610, Article, Mass Spectrometry, Epigenesis, Genetic, Histones, Mice, Cytidine Deaminase, Animals, In Situ Hybridization, Fluorescence, DNA Primers, B-Lymphocytes, Flow Cytometry, Immunoglobulin Class Switching, Mice, Mutant Strains, Immunoglobulin Switch Region, Mice, Inbred C57BL, Chromobox Protein Homolog 5, Chromatography, Gel
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