A role of Bcl6 in induction of somatic hypermutation in immunoglobulin gene
| Project/Area Number |
16390140
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Immunology
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| Research Institution | Chiba University |
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Principal Investigator |
TAKESHI Tokuhisa Chiba University, Graduate School of Medicine, Professor, 大学院・医学研究院, 教授 (20134364)
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| Co-Investigator(Kenkyū-buntansha) |
HATANO Masahiko Chiba University, Gene Research Center, Associate Prof., バイオメディカル研究センター, 助教授 (20208523)
ARIMA Masafumi Chiba University, Graduate School of Medicine, Lecturer, 大学院・医学研究院, 講師 (00202763)
SAKAMOTO Akemi Chiba University, Graduate School of Medicine, Assistant Prof., 大学院・医学研究院, 助手 (90359597)
FUJIMURA Liza Chiba University, Graduate School of Medicine, Assistant Prof., バイオメディカル研究センター, 助手 (30376363)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 2005: ¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 2004: ¥8,500,000 (Direct Cost: ¥8,500,000)
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| Keywords | Bcl6 / somatic hypermutation / ADAR1 / immunoglobulin class-switch region / germinal center B cells / memory B cells / class-switch / gene-deficient mice |
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| Research Abstract |
Bcl6 is highly expressed in germinal center B cells and is essential for development of high affinity memory B cells. Bcl6 functions as a sequence specific transcriptional repressor by recruiting a histone deacetylase complex. However, the role for Bcl6 in somatic hypermutation (SHM) of immunoglobulin genes is largely unknown. Here we show that SHM with two hot spots was detected in the immunoglobulin class-switch region of various cells from Bcl6-deficient mice. These hot spot SHMs were generated by conversion of adenine to guanine. Adenosine deaminase acting on RNA-1 (ADAR1) mRNA was overexpressed in various cells from Bcl6-deficient mice but repressed in lck-Bcl6 transgenic mice, and three Bcl6-binding sequences were identified in the promoter region of the ADAR1 gene, indicating that ADAR1 is a molecular target of Bcl6. Overexpression of ADAR1 triggered the SHMs in normal cells. Furthermore, histone acetylation was observed in the hot spot region of Bcl6-deficient cells whereas Bcl6 bound near the region to deacetylate regional histones in normal cells. Thus, ADAR1 can induce SHM in germ line DNA with chromatin modifications, and Bcl6 inhibits the ADAR1-induced SHM especially in germinal center B cells.
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Report
(3 results)
Research Products
(25 results)
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[Journal Article] Pkd1 regulates immortalized proliferation of renal tubular epithelial cells through induction of P53 and activation of JNK.2005
Author(s)
Nishio, S., Hatano, M., Nagata, M., Horie, S., Koike, T., Tokuhisa, T., Mochizuki, T.
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Journal Title
J.Clin.Invest. 115
Pages: 910-918
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] A role for c-Fos/AP-1 in B lymphocyte terminal differentiation.2005
Author(s)
Ohkubo, Y., Arima, M., Arguni, E., Okada, S., Yamashita, K., Asari, S., Obata, S., Sakamoto, A., Hatano, M., O-Wang, J., Ebara, M., Saisho, H., Tokuhisa, T.
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Journal Title
J.Immunol. 174
Pages: 7703-7710
Description
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[Journal Article] DNA polymerase (theta) contributes to the generation of C/G mutations during somatic hypermutation of Ig genes.2005
Author(s)
Masuda, K., Ouchida, R., Takeuchi, A., Saito, T., Koseki, H., Kawamura, K., Tagawa, M., Tokuhisa, T., Azuma, T., Jiyang O-Wang, J.
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Journal Title
Proc.Natl.Acad.Sci.USA. 102
Pages: 13986-13991
Description
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[Journal Article] Abnormal erythroid differentiation in neonatal Bcl6-deficient mice.2004
Author(s)
Asari, S., Sakamoto, A., Okada, S., Ohkubo, Y, Arima, M., Hatano, M., Kuroda, K., Tokuhisa, T.
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Journal Title
Transplantation 78
Pages: 516-523
Description
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[Journal Article] Role of autophagy during the early neonatal starvation period.2004
Author(s)
Kuma, A., Hatano, M., Matsui, M., Yamamoto, A., Nakaya, H., Yoshimori, T., Ohsumi, Y., Tokuhisa, T., Mizushima, N.
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Journal Title
Nature 432
Pages: 1032-1036
Description
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