| Project/Area Number |
18390149
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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 |
TOKUHISA Takeshi Chiba University, Graduate School of Medicine, Professor (20134364)
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| Co-Investigator(Kenkyū-buntansha) |
HATANO Masahiko Chiba University, Graduate School of Medicine, Professor (20208523)
ARIMA Masafumi Chiba University, Graduate School of Medicine, Lecturer (00202763)
SAKAMOTO Akemi Chiba University, Graduate School of Medicine, Assistant Prof. (90359597)
FUJIMURA Risa Chiba University, Biomedical Center, Assistant Prof. (30376363)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥16,720,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥1,920,000)
Fiscal Year 2007: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
Fiscal Year 2006: ¥8,400,000 (Direct Cost: ¥8,400,000)
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| Keywords | immunology / target gene / cancer / genome / gene regulation |
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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, a role for Bcl6 in induction of somatic hypermutation in germinal center B cells is not known. When we examined mutation frequencies in the Ig class-switch region and the c-myc region of IgG1 B cells derived from Bcl6-deficient mice, the frequencies in Bcl6-deficient IgG1 B cells were higher than those in wild type IgG1 B cells. These mutations were mainly generated by conversion of adenine to guanine. RNA-editing adenosine deaminase (ADAR) family converts adenosine of pre-mRNA into inosine, which is subsequently translated as guanosine, and ADAR1 mRNA among ADAR family was overexpressed in various cells from Bcl6-deficient mice. The promoter analysis revealed that ADAR1 is a molecular target of Bcl6. Furthermore, the exogenous ADAR1 increased frequency of point mutations from adenine to guanine in those regions of wild type IgG1 B cells. Since ADAR1 mRNA is detected in germinal center B cells in spite of high Bcl6 expression, ADAR1 may contribute adenine-targeted somatic hypermutation in germinal center B cells.
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