| Project/Area Number |
26460355
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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 | Tohoku University |
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Principal Investigator |
TANABE OSAMU 東北大学, 東北メディカル・メガバンク機構, 教授 (70221398)
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| Co-Investigator(Kenkyū-buntansha) |
鈴木 未来子 東北大学, 医学系研究科, 講師 (80508309)
横澤 潤二 東北大学, 東北メディカル・メガバンク機構, 非常勤講師 (10722605)
西川 慧 東北大学, 東北メディカル・メガバンク機構, 研究支援者 (40722616)
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| Project Period (FY) |
2014-04-01 – 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 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | βグロビン異常症 / 胚型εグロビン / 胎児型γグロビン / 遺伝子発現制御 / DNAメチル基転移酵素1 / 核内受容体 / TR2 / TR4 / ノックアウトマウス / 赤血球 / ヒストン修飾 / DNAメチル化 / エピジェネティクス / ヘモグロビンスイッチング / グロビンスイッチング |
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| Outline of Final Research Achievements |
Re-induction of embryonic or fetal hemoglobin has therapeutic effects for patients with beta-globin disorders such as beta-thalassemia and sickle cell disease. For the development of therapeutic agents with such effects, the elucidation of the molecular mechanisms for the inactivation of those genes in adult is crucial. In this study, we demonstrated that DNA methyltransferase 1 (DNMT1) is essential for the inactivation of the embryonic beta-type globin gene in adult erythroid cells. Furthermore, we demonstrated that nuclear receptors TR2 and TR4 are essential for the inactivation of the embryonic and fetal beta-type globin genes, as well as for the recruitment of DNMT1 to the promoters of these genes in adult erythroid cells. These results indicate the critical roles of DNMT1 in the inactivation of the embryonic and fetal beta-type globin genes in adult, which is elicited by TR2 and TR4.
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