Regulation of histone H4 acetylation by transcription factor E2A in Ig gene conversion.
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.
Kitao
Hiroyuki
H
Department of Late Effect Studies, Radiation Biology Center, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Kimura
Masayo
M
Yamamoto
Kazuhiko
K
Seo
Hidetaka
H
Namikoshi
Keiko
K
Agata
Yasutoshi
Y
Ohta
Kunihiro
K
Takata
Minoru
M
D000107:Acetylation; D000818:Animals; D030161:Avian Proteins / Q000235:genetics / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002645:Chickens; D047369:Chromatin Immunoprecipitation; D003564:Cytidine Deaminase / Q000378:metabolism; D005785:Gene Conversion; D005786:Gene Expression Regulation; D005803:Genes, Immunoglobulin / Q000235:genetics*; D006657:Histones / Q000378:metabolism*; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D030161:Avian Proteins; D051792:Basic Helix-Loop-Helix Proteins; D003564:Cytidine Deaminase; D006657:Histones; D000098830:AICDA (Activation-Induced Cytidine Deaminase)