ゲノム認識エピジェネティック変更化合物の開発
Publicly Offered Research
Project Area | Analyses and regulation of germline epigenome |
Project/Area Number |
26112517
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Research Category |
Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
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Allocation Type | Single-year Grants |
Review Section |
Biological Sciences
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Research Institution | Chiba Cancer Center (Research Institute) |
Principal Investigator |
永瀬 浩喜 千葉県がんセンター(研究所), がん遺伝創薬研究室, 研究所長 (90322073)
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Project Period (FY) |
2014-04-01 – 2016-03-31
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Project Status |
Completed (Fiscal Year 2015)
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Budget Amount *help |
¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
Fiscal Year 2015: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2014: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
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Keywords | ヒストン脱アセチル化酵素阻害剤 / エピゲノム変更 / DNA配列認識化合物 / ピロールイミダゾールポリアミド / ヒストンアセチル化酵素活性化剤 / リプログラミング / 多能性幹細胞誘導 / エピジェネティクス / エピゲノム / 化学バイオプローブ / ヒストン脱アセチル化阻害剤 |
Outline of Annual Research Achievements |
本研究課題では、領域研究者の希望するゲノム領域に本技術による配列特異的な転写阻害剤PIP やエピゲノム変更薬PIP-SAHA、PIP-CBI等をデザイン・合成し供給していくことおよび他のヒストン修飾阻害剤とのコンジュゲートを合成し、新たな標的領域特異的なエピゲノム変更技術を確立することを目的とした。このことで、領域研究者による生殖細胞のエピゲノムの乱れの機能解析に役立て、エピゲノムを正常化する薬剤候補を開発・提供できるよう研究を進めた。 具体的にはDNA結合化合物(PIP)によるヒストン脱アセチル化酵素阻害剤(SAHA)を生殖細胞、幹細胞に送達させることの確認および作成したPIP-SAHAライブラリーによりヒト繊維芽細胞への化合物の効果を確認し、それぞれの化合物が誘導する遺伝子発現の変化を確認した。特に多能性幹細胞様の発現パターンをヒト皮膚繊維芽細胞で導く化合物E、F、H、Iについてその発現誘導とPIPのゲノム結合領域の予測による作用機序の解明を試み、幹細胞誘導因子と関連する遺伝子ネットワークの活性化を確認した。またPIP化合物が、マウス精巣細胞及び卵巣細胞内に送達されることも確認した。今後、生殖エピゲノムを化合物により変更する技術を開発し、学術領域の発展に貢献できれば幸いである。
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Research Progress Status |
27年度が最終年度であるため、記入しない。
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Strategy for Future Research Activity |
27年度が最終年度であるため、記入しない。
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Report
(2 results)
Research Products
(27 results)
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[Journal Article] Genetic alterations in Japanese extrahepatic biliary tract cancer.2016
Author(s)
Noguchi R, Yamaguchi K, Ikenoue T, Terakado Y, Ohta Y, Yamashita N, Kainuma O, Yokoi S, Maru Y, Nagase H, Furukawa Y.
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Journal Title
Oncology Letters
Volume: -
Related Report
Peer Reviewed
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[Journal Article] Targeting Oct1 genomic function inhibits androgen receptor signaling and castration-resistant prostate cancer growth2016
Author(s)
Inoue S, Obinata D, Takayama K, Urano T, Suzuki T, Takahashi S, Fujimura T, Homma Y, Fujiwara K, Fukuda N, Nagase H, Aburatani H, and Tsutsumi S.
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Journal Title
Related Report
Peer Reviewed
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[Journal Article] Preclinical Study of Novel Gene Silencer Pyrrole-Imidazole Polyamide Targeting Human TGF-β1 Promoter for Hypertrophic Scars in a Common Marmoset Primate Model.2015
Author(s)
Igarashi J, Fukuda N, Inoue T, Nakai S, Saito K, Fujiwara K, Matsuda H, Ueno T, Matsumoto Y, Watanabe T, Nagase H, Bando T Sugiyama H Itoh T Soma M.
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Journal Title
PlosOne.
Volume: 10(5)
Issue: 5
Pages: e0125295-e0125295
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Pyrrole-Imidazole (PI) polyamide-mediated silencing of KCNQ1OT1 expression induces cell death in Wilms tumor cells.2015
Author(s)
Yoshizawa S, Fujiwara K, Sugito K, Uekusa S, Kawashima H, Hoshi R, Watanabe Y, Hirano T, Furuya T, Masuko T, Ueno T, Fukuda N, Soma M, Ozaki T, Koshinaga T, Nagase H.
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Journal Title
International Journal of Oncology
Volume: 47(1)
Issue: 1
Pages: 115-121
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Identification of a novel E-box binding PI polyamide inhibiting MYC-driven cell-proliferation.2015
Author(s)
Mishra R, Watanabe T, Kimura M, Koshikawa N, Ikeda M, Uekusa S, Kawashima H, Wang X, Igarashi J, Choudhury D, Grandori C, Kemp C, Ohira M, Verma N, Kobayashi Y, Takeuchi J, Koshinaga T, Nemoto N, Fukuda N, Soma M, Kusafuka T, Fujiwara K, Nagase H.
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Journal Title
Cancer Science
Volume: 106(4)
Issue: 4
Pages: 421-429
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Inhibition of KRAS codon 12 mutants using a novel DNA-alkylating pyrrole-imidazole polyamide conjugate.2014
Author(s)
Hiraoka K, Inoue T, Taylor RD, Watanabe T, Koshikawa N, Yoda H, Shinohara K, Takatori A, Sugimoto H, Maru Y, Denda T, Fujiwara K, Balmain A, Ozaki T, Bando T, Sugiyama H, Nagase H.
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Journal Title
Nat. Commun.
Volume: 6
Issue: 1
Pages: 6706-6706
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Inhibition of malignant phenotypes of human osteosarcoma cells by a gene silencer, a pyrrole-imidazole polyamide, which targets E-box.2014
Author(s)
134. Taniguchi M, Nakai Y, Ozaki T, Koshikawa N, Kojima T, Kataba M, Oguni A, Matsuda H, Yoshida Y, Tokuhashi Y, Fukuda N, Ueno T, Soma T, Nagase H.
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Journal Title
FEBS Open Bio
Volume: 4
Issue: 1
Pages: 328-334
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] A novel gene regulator, pyrrole-imidazole polyamide targeting ABCA1 gene increases cholesterol efflux from macrophages and plasma HDL concentration2014
Author(s)
Tsunemi A, Ueno T, Fukuda N, Watanabe T, Tahira K, Haketa A, Hatanaka Y, Tanaka S, Matsumoto T, Matsumoto Y, Nagase H, Soma M
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Journal Title
Journal of Molecular Medicine
Volume: 92
Issue: 5
Pages: 509-521
DOI
Related Report
Peer Reviewed
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[Journal Article] Inhibition of Human Osteosarcoma Cell Migration and Invasion by a Gene Silencer, Pyrrole–Imidazole Polyamide, Targeted at the Human MMP9 NF-κB Binding Site2014
Author(s)
Kojima T, Wang X, Fujiwara K, Osakaa S, Yoshida Y, Osaka E, Taniguchi M, Ueno T, Fukuda N, Soma M, Tokuhashi Y and Nagase H.
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Journal Title
Biological and Pharmaceutical Bulletin
Volume: 37
Issue: 9
Pages: 1460-1465
DOI
NAID
ISSN
0918-6158, 1347-5215
Related Report
Peer Reviewed / Open Access
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[Journal Article] Pyrrole-imidazole polyamide targeted to break fusion sites in TMPRSS2 and ERG gene fusion represses prostate tumor growth2014
Author(s)
Obinata D, Ito Akiko, Fujiwara K, Takayama K, Ashikari D, Murata Y, Yamaguchi K, Urano T, Fujimura T, Fukuda N, Soma M, Watanabe T, Nagase H, Inoue S, Takahashi S
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Journal Title
Cancer Sci
Volume: 105
Issue: 10
Pages: 1272-1278
DOI
Related Report
Peer Reviewed / Open Access
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