| Project/Area Number |
15K08285
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | Takasaki University of Health and Welfare |
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Principal Investigator |
Kinuko Ohneda 高崎健康福祉大学, 薬学部, 教授 (50323291)
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| Co-Investigator(Kenkyū-buntansha) |
石嶋 康史 高崎健康福祉大学, 薬学部, 講師 (10433640)
大森 慎也 高崎健康福祉大学, 薬学部, 助教 (10509194)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 転写因子 / マスト細胞 / プロテアーゼ / 遺伝子発現 / 遺伝子発現制御 / トリプターゼ |
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| Outline of Final Research Achievements |
Mouse mast cell tryptase genes (Tpsg1, Tpsb2 and Tpsab1) are located at chromosome 17A3.3. In this study, we examined molecular basis of mast cell tryptase gene regulation by GATA1 and GATA2. Quantitative RT-PCR analysis showed that tryptase gene mRNA levels were significantly reduced by the loss of GATA factors in bone marrow mast cells (BMMCs). ChIP assays revealed that the GATA factors bind to the regions located at 72.8 and 84.3 kb upstream of Tpsb2 gene (referred to as region A and region B) in BMMCs. Deletion of region A using the CRISPR/Cas9 system resulted in a significant reduction of the Tpsb2 and Tpsg1 mRNA levels in MEDMC-BRC6 mast cells. Furthermore, CTCF and the cohesin subunit Rad21 binding to the regions between regions A and B was significantly reduced by the loss of GATA1 in BMMCs. Collectively, these results suggest that GATA factors play important roles for organizing active chromatin architecture at mouse tryptase genomic locus in mast cells.
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