Epigenetic tethering of AID to the donor switch region during immunoglobulin class switch recombination

J Exp Med. 2011 Aug 1;208(8):1649-60. doi: 10.1084/jem.20110118. Epub 2011 Jul 11.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / immunology
  • Blotting, Western
  • Chromatin Immunoprecipitation
  • Chromatography, Gel
  • Chromobox Protein Homolog 5
  • Chromosomal Proteins, Non-Histone / metabolism
  • Cytidine Deaminase / immunology*
  • DNA Mutational Analysis
  • DNA Primers / genetics
  • Epigenesis, Genetic / immunology*
  • Flow Cytometry
  • Histones / metabolism
  • Immunoglobulin Class Switching / immunology*
  • Immunoglobulin Switch Region / immunology*
  • In Situ Hybridization, Fluorescence
  • Mass Spectrometry
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Nuclear Proteins / genetics
  • Nuclear Proteins / immunology*
  • Nuclear Proteins / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / immunology*
  • Repressor Proteins / metabolism
  • Tripartite Motif-Containing Protein 28


  • Chromosomal Proteins, Non-Histone
  • DNA Primers
  • Histones
  • Nuclear Proteins
  • Repressor Proteins
  • Chromobox Protein Homolog 5
  • Trim28 protein, mouse
  • Tripartite Motif-Containing Protein 28
  • AICDA (activation-induced cytidine deaminase)
  • Cytidine Deaminase