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

被引：20

作者：

Kitao, Hiroyuki ^{[1
]}

Kimura, Masayo ^{[3
]}

Yamamoto, Kazuhiko ^{[3
]}

Seo, Hidetaka ^{[2
]}

Namikoshi, Keiko ^{[3
]}

Agata, Yasutoshi ^{[4
]}

Ohta, Kunihiro ^{[5
]}

Takata, Minoru ^{[1
]}

机构：

[1] Kyoto Univ, Dept Late Effect Studies, Ctr Radiat Biol, Sakyo Ku, Kyoto 6068501, Japan

[2] Chiome Biosci Inc, Kyoto 1130033, Japan

[3] Kawasaki Med Sch, Dept Immunol & Mol Genet, Okayama 7010192, Japan

[4] Osaka Med Ctr Maternal & Child Hlth, Res Inst, Dept Dev Infect Dis, Izumi, Osaka 5941101, Japan

[5] Univ Tokyo, Grad Sch Arts & Sci, Dept Life Sci, Tokyo 1538902, Japan

来源：

INTERNATIONAL IMMUNOLOGY | 2008年 / 20卷 / 02期

关键词：

activation-induced deaminase; chromatin immunoprecipitation; DT40 cell line; ACTIVATION-INDUCED DEAMINASE; SOMATIC HYPERMUTATION; HOMOLOGOUS RECOMBINATION; AID GENE; IMMUNOGLOBULIN; CHAIN; EXPRESSION; PROTEINS; REPAIR; CELLS;

D O I：

10.1093/intimm/dxm140

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：277 / 284

页数：8

共 30 条

[1] Immunoglobulin gene conversion: Insights from bursal B cells and the DT40 cell line [J].

Arakawa, H ;

Buerstedde, JM .

DEVELOPMENTAL DYNAMICS, 2004, 229 (03) :458-464

[2] Mutants IoxP vectors for selectable marker recycle and conditional knock-outs [J].

Arakawa H. ;

Lodygin D. ;

Buerstedde J.-M. .

BMC Biotechnology, 1 (1)

[3] Requirement of the activation-induced deaminase (AID) gene for immunoglobulin gene conversion [J].

Arakawa, H ;

Hauschild, J ;

Buerstedde, JM .

SCIENCE, 2002, 295 (5558) :1301-1306

[4] Regulation of E2A activities by histone acetyltransferases in B lymphocyte development [J].

Bradney, C ;

Hjelmeland, M ;

Komatsu, Y ;

Yoshida, M ;

Yao, TP ;

Zhuang, Y .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (04) :2370-2376

[5] XRCC3 controls the fidelity of homologous recombination: Roles for XRCC3 in late stages of recombination [J].

Brenneman, MA ;

Wagener, BM ;

Miller, CA ;

Allen, C ;

Nickoloff, JA .

MOLECULAR CELL, 2002, 10 (02) :387-395

[6]

Buerstedde Jean-Marie, 2006, Subcell Biochem, V40, P11

[7] INCREASED RATIO OF TARGETED TO RANDOM INTEGRATION AFTER TRANSFECTION OF CHICKEN B-CELL LINES [J].

BUERSTEDDE, JM ;

TAKEDA, S .

CELL, 1991, 67 (01) :179-188

[8] LIGHT CHAIN GENE CONVERSION CONTINUES AT HIGH-RATE IN AN ALV-INDUCED CELL-LINE [J].

BUERSTEDDE, JM ;

REYNAUD, CA ;

HUMPHRIES, EH ;

OLSON, W ;

EWERT, DL ;

WEILL, JC .

EMBO JOURNAL, 1990, 9 (03) :921-927

[9] The chicken Ig light chain 3′-enhancer is essential for gene expression and regulates gene conversion via the transcription factor E2A [J].

Conlon, TM ;

Meyer, KB .

EUROPEAN JOURNAL OF IMMUNOLOGY, 2006, 36 (01) :139-148

[10] Chromatin structure regulates gene conversion [J].

Cummings, W. Jason ;

Yabuki, Munehisa ;

Ordinario, Ellen C. ;

Bednarski, David W. ;

Quay, Simon ;

Maizels, Nancy .

PLOS BIOLOGY, 2007, 5 (10) :2145-2155

← 1 2 3 →