| Project/Area Number |
13671743
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Keio University |
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Principal Investigator |
MARUYAMA Tetsuo School of Medicine, Keio University / Department of Obstetrics and Gynecology / Assistant Professor, 医学部, 専任講師 (10209702)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMIZU Aki School of Medicine, Keio University / Department of Obstetrics and Gynecology / instructor, 医学部, 助手 (60306826)
山本 百合恵 慶應義塾大学, 医学部, 助手 (00286543)
酒井 のぞみ 慶應義塾大学, 医学部, 助手 (60276326)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2002: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2001: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | endometrium / decidualization / histone acetylation / estrogen / progesterone / differentiation / trichostatin A / insulin-like growth factor binding protein-1 / コアヒストン / プロラクチン |
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| Research Abstract |
Histone acetyltransferases and histone deacetylases (HDACs) determine the acetylation status of histones, regulating gene transcription. Decidualization is the progestin-induced differentiation of estrogen-primed endometrial stromal cells (ESCs), which is crucial for implantation and maintenance of pregnancy. We here show that trichostatin A (TSA), a specific HDAC inhibitor, enhances the up-regulation of decidualization markers such as insulin-like growth factor binding protein-1 (IGFBP-1) and prolactin in a dose-dependent manner that is directed by 17β-estradiol (E2) plus progesterone (P4) in cultured ESCs, but not glandular cells, both isolated from human endometrium. Morphological changes resembling decidual transformation were also augmented by co-addition of TSA. Acid urea triton gel analysis and immunoblot using acetylated histone type specific antibodies demonstrated that treatment with E2 plus P4 significantly increased the levels of acetylated H3 and H4 whose increment was augmented by cotreatment with TSA. Individual HATs are known to possess acetylation preferences for specific sites and substrates. Given the acetylation sites upon treatment with ovarian steroids as demonstrated in this study, SRC-1 and CBP/p300 may be likely candidates for HATs responsible for histone acetylation in the process of decidualization. Chromatin immunoprecipitation assay revealed that treatment with E2 plus P4 increased the amount of proximal progesterone-responsive region of IGFBP-1 promoter associated with acetylated H4, which was dramatically enhanced by co-addition of TSA. Taken together, our results suggest that histone acetylation is deeply involved in differentiation of human ESCs and that TSA has a potential as an enhancer of decidualization through promotion of progesterone action
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