Regulation of histone H4 acetylation by transcription factor E2A in Ig gene conversion.

Hiroyuki Kitao, Masayo Kimura, Kazuhiko Yamamoto, Hidetaka Seo, Keiko Namikoshi, Yasutoshi Agata, Kunihiro Ohta, Minoru Takata

Department of Late Effect Studies, Radiation Biology Center, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.

International immunology 2008 Feb

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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.

Citation

Hiroyuki Kitao, Masayo Kimura, Kazuhiko Yamamoto, Hidetaka Seo, Keiko Namikoshi, Yasutoshi Agata, Kunihiro Ohta, Minoru Takata. Regulation of histone H4 acetylation by transcription factor E2A in Ig gene conversion. International immunology. 2008 Feb;20(2):277-84