| Project/Area Number |
26350977
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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 |
Chemical biology
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| Research Institution | Chiba University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
KANEDA Atsushi 千葉大学, 大学院医学研究院, 教授 (10313024)
NEMOTO Tetsuhiro 千葉大学, 大学院薬学研究院, 特任助教 (80361450)
SUZUKI Takayoshi 京都府立医科大学, 大学院医学研究科, 教授 (90372838)
SUGIYAMA Hiroshi 京都大学, 大学院理学研究科, 教授 (50183843)
NAGASE Hiroki 千葉県がんセンター, 研究所, 所長 (90322073)
WATANABE Takayoshi 千葉県がんセンター, 研究所, 研究員 (60526060)
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| Research Collaborator |
YODA Natsumi
FUKUYO Masaki
TAKANE Kiyoko
FUJIWARA Kyoko
KITA Kazuko
FUKUDA Noboru
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2015: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | ピロール・イミダゾール・ポリアミド / 核酸化学 / 発現制御 / エピゲノム / ヒストンメチル化 / DNA配列認識 / エピゲノム制御 / ピロール・イミダゾールポリアミド / ピロール-イミダゾールポリアミド / エピジェネティクス |
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| Outline of Final Research Achievements |
Aberrant DNA methylation and histone modification cause major epigenetic changes and have been implicated in cancer growth. While drugs for epigenome such as SAHA and decitabine can be available for cancer treatment, site-specific modification of epigenome is now requested to be technically achieved. Pyrrole-imidazole polyamides are small molecules that can be designed to recognize and bind to particular DNA sequences. In this study, we synthesized PIP-LSD1 inhibitor conjugates and investigated whether the conjugates show site-selective changing of histone methylation. The results in this study indicate that PIP-inhibitor conjugates induced histone methylation where single inhibitor could not change. In addition, it is shown that PIP can act as sequence-specific antagonists of CpG methylation in living cells.
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