Open AccessRegulation of histone H4 acetylation by transcription factor E2A in Ig gene conversion
Author(s) -
Hiroyuki Kitao,
Masayo Kimura,
Kazuhiko Yamamoto,
Hyemyung Seo,
Keiko Namikoshi,
Yasutoshi Agata,
Kunihiro Ohta,
Minoru Takata
Publication year - 2008
Publication title -
international immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.86
H-Index - 134
eISSN - 1460-2377
pISSN - 0953-8178
DOI - 10.1093/intimm/dxm140
Subject(s) - somatic hypermutation , trichostatin a , histone h4 , microbiology and biotechnology , chromatin immunoprecipitation , acetylation , histone h2a , histone , histone methyltransferase , biology , chromatin , cytidine deaminase , chemistry , gene , genetics , gene expression , promoter , histone deacetylase , b cell , antibody
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.
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