| Project/Area Number |
25670643
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Kyoto University |
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Principal Investigator |
KATO Tomohisa 京都大学, 再生医科学研究所, 講師 (50301247)
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| Co-Investigator(Kenkyū-buntansha) |
TOGUCHIDA Junya 京都大学, 再生医科学研究所, 教授 (40273502)
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| Project Period (FY) |
2013-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2013: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
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| Keywords | 滑膜肉腫 / エピジェネティクス / 遺伝子発現制御 / クロマチン修飾 / タンパク質間相互作用 / がんの起源細胞 |
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| Research Abstract |
We have been trying to unravel the molecular mechanism underlying the transcriptional dysregulation of FZD10 gene in synovial sarcomas (SSs) and have found that histone acetylation of the promoter region of FZD10 strongly correlates with up-regulation of FZD10 in SS. So, we next aimed to identify the histone acetyltransferase (HAT) responsible for this. By adopting pull-down assay followed by Western blotting, we succeeded to identify two HATs (designated as SSIH1 and 2) as the interactors of SS18-SSX. Furthermore, by using dominant-negative (DN) forms of SSIH1 and SSIH2, we have demonstrated that ectopic expression of SSIH(DN) in SS cells abrogated the expression of FZD10. This result indicates SSIH1 and SSIH2 are functionally involved in up-regulation of FZD10 in SSs, However, ChIP assay revealed that only SSHI1 occupies the FZD10 promoter region in vivo. Collectively, We have identified SSIH1 as the HAT responsible for the FZD10 dysregulation in SSs.
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