International Immunology Advance Access originally published online on January 7, 2008
International Immunology 2008 20(2):277-284; doi:10.1093/intimm/dxm140
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Regulation of histone H4 acetylation by transcription factor E2A in Ig gene conversion
1 Department of Late Effect Studies, Radiation Biology Center, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
2 Department of Immunology and Molecular Genetics, Kawasaki Medical School, Okayama 701-0192, Japan
3 Chiome Bioscience Inc., Tokyo 113-0033, Japan
4 Department of Developmental Infectious Diseases, Research Institute, Osaka Medical Center for Maternal and Child Health, Izumi-shi, Osaka 594-1101, Japan
5 Department of Life Sciences, Graduate School of Arts and Sciences, University of Tokyo, Tokyo 153-8902, Japan
6 Present address: Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-5885, Japan
Correspondence to: M. Takata; E-mail: mtakata{at}house.rbc.kyoto-u.ac.jp
Recent studies implicate the transcription factor E2A in Ig diversification such as somatic hypermutation or gene conversion (GCV). GCV also requires active Ig transcription, expression of the activation-induced deaminase (AID) and a set of homologous recombination factors. We have disrupted the E2A gene in the chicken B-cell line DT40 and found greatly diminished rate of GCV without changes in the levels of transcripts from AID and Ig heavy chain or Ig light chain (IgL) genes. However, chromatin immunoprecipitation analysis revealed that the loss of E2A accompanies drastically reduced acetylation levels of the histone H4 in rearranged IgL locus. Furthermore, the defects in GCV were restored by trichostatin A treatment, which raised H4 acetylation to the normal levels. Thus, E2A may contribute to GCV by maintaining histone acetylation, which could be a prerequisite for targeting or full deaminase function of AID.
Keywords: activation-induced deaminase, chromatin immunoprecipitation, DT40 cell line
* These authors contributed equally to this study.
Transmitting editor: T. Kurosaki
Received 5 September 2007, accepted 30 November 2007.
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