Identification and regulation mechanism of enhancers for hematopoietic cell fate decision
Project/Area Number |
16K09846
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Hematology
|
Research Institution | Shiga University of Medical Science |
Principal Investigator |
|
Research Collaborator |
Tatsumi Goichi
Asai Ai
|
Project Period (FY) |
2016-04-01 – 2019-03-31
|
Project Status |
Completed (Fiscal Year 2018)
|
Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
Keywords | 白血病 / 造血分化 / エンハンサー / ヒストン修飾 / LSD1 / 転写因子 |
Outline of Final Research Achievements |
In the current study, we found that several enhancers which regulate transcription factors involved in hematopoiesis are suppressed in leukemia cells. The interaction between transcription factors and a histone modifier LSD1 is indispensable in suppression of the enhancers. Disruption of the interaction caused the induction of myeloid differentiation in leukemia cells. However, the myeloid differentiation was impaired by knockout of the enhancers. Collectively, the interaction between transcription factors and LSD1 on the enhancers plays an important role in the sustenance of leukemia.
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Academic Significance and Societal Importance of the Research Achievements |
白血病は、蛋白をコードする遺伝子の変異の積み重ねによって生じ、そうした変異を標的とした新規薬剤の開発が近年進められている。しかし我々の研究は、エンハンサーと呼ばれる遺伝子本体の外側にあるゲノム領域が異常に制御されると、遺伝子発現プログラムが変化し、白血病の維持に関わるらしいことを明らかにした。そして、エンハンサーを抑制するメカニズムが、白血病治療の新たな標的となりうることを明らかにした。
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Report
(4 results)
Research Products
(28 results)
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[Journal Article] Astaxanthin, a xanthophyll carotenoid, prevents development of dextran sulphate sodium-induced murine colitis2019
Author(s)
Sakai S, Nishida A, Ohno M, Inatomi O, Bamba S, Sugimoto M, Kawahara M, Andoh A.
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Journal Title
Journal of Clinical Biochemistry and Nutrition
Volume: 64
Issue: 1
Pages: 66-72
DOI
NAID
ISSN
0912-0009, 1880-5086
Related Report
Peer Reviewed
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[Journal Article] Ameliorating effects of bortezomib, a proteasome inhibitor, on development of dextran sulfate sodium-induced murine colitis2018
Author(s)
Sakai S, Nishida A, Ohno M, Inatomi O, Bamba S, Sugimoto M, Kawahara M, Andoh A.
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Journal Title
Journal of Clinical Biochemistry and Nutrition
Volume: 63
Issue: 3
Pages: 217-223
DOI
ISSN
0912-0009, 1880-5086
Related Report
Peer Reviewed
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[Journal Article] Magnified single-balloon enteroscopy in the diagnosis of intestinal follicular lymphoma: a case series.2018
Author(s)
Takahashi K, Bamba S, Kawahara M, Nishida A, Inatomi O, Sasaki M, Tsujikawa T, Kushima R, Sugimoto M, Kitoh K, Andoh A.
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Journal Title
Intest Res.
Volume: 16
Issue: 4
Pages: 628-634
DOI
Related Report
Peer Reviewed
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[Journal Article] A novel mutation causing type 1 Gaucher disease found in a Japanese patient with gastric cancer: A case report.2018
Author(s)
Hosoba S, Kito K, Teramoto Y, Adachi K, Nakanishi R, Asai A, Iwasa M, Nishimura R, Moritani S, Kawahara M, Minamiguchi H, Nanba E, Kushima R, Andoh A.
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Journal Title
Medicine (Baltimore)
Volume: 97
Issue: 27
Pages: e11361-e11361
DOI
Related Report
Peer Reviewed
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[Journal Article] MicroRNA-33 regulates the population of peripheral inflammatory Ly6Chigh monocytes through dual pathways.2018
Author(s)
Baba O, Horie T, Hakuno D, Nakashima Y, Nishi H, Kuwabara Y, Nakao T, Nishiga M, Nishino T, Ide Y, Nakazeki F, Koyama S, Kimura M, Hanada R, Kawahara M, Kimura T, and Ono K.
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Journal Title
Mol Cell Biol.
Volume: 38
Issue: 14
Pages: 1-17
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] 初診時脳内出血を伴う急性骨髄性白血病の中枢神経病変管理における髄液細胞数モニタリングの有用性.2018
Author(s)
河原 真大, 寺本 由加子, 浅井 愛, 永井 詩穂, 岩佐 磨佐紀, 藤城 綾, 西村 理恵, 南口 仁志, 辻 篤司, 木藤 克之, 安藤 朗.
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Journal Title
臨床血液
Volume: 59
Pages: 2578-2582
NAID
Related Report
Peer Reviewed
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[Journal Article] Analysis of endoscopic brush samples identified mucosa-associated dysbiosis in inflammatory bowel disease.2018
Author(s)
Nishino K, Nishida A, Inoue R, Kawada Y, Ohno M, Sakai S, Inatomi O, Bamba S, Sugimoto M, Kawahara M, Naito Y, Andoh A
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Journal Title
J Gastroenterol.
Volume: 53
Issue: 1
Pages: 95-106
DOI
Related Report
Peer Reviewed
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[Journal Article] Expression of Interleukin-26 is upregulated in inflammatory bowel disease.2017
Author(s)
Fujii M, Nishida A, Imaeda H, Ohno M, Nishino K, Sakai S, Inatomi O, Bamba S, Kawahara M, Shimizu T, Andoh A
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Journal Title
World J Gastroenterol.
Volume: 23
Issue: 30
Pages: 5519-5529
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] A novel LSD1 inhibitor NCD38 ameliorates MDS-related leukemia with complex karyotype by attenuating leukemia programs via activating super-enhancers.2017
Author(s)
Sugino N, Kawahara M, Tatsumi G, Kanai A, Matsui H, Yamamoto R, Nagai Y, Fujii S, Shimazu Y, Hishizawa M, Inaba T, Andoh A, Suzuki T, Takaori-Kondo A.
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Journal Title
Leukemia
Volume: in press
Issue: 11
Pages: 2303-2314
DOI
Related Report
Peer Reviewed
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[Journal Article] Hypomethylation of the Treg-specific demethylated region in FOXP3 is a hallmark of the regulatory T-cell subtype in adult T-cell leukemia2016
Author(s)
Shimazu Y, Shimazu Y, Hishizawa M, Hamaguchi M, Nagai Y, Sugino N, Fujii S, Kawahara M, Kadowaki N, Nishikawa H, Sakaguchi S, Takaori-Kondo A
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Journal Title
Cancer Immunol Res
Volume: 4
Issue: 2
Pages: 136-145
DOI
Related Report
Peer Reviewed
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[Presentation] 当院における用量調整VRD療法2017
Author(s)
Asai A, Nagai S, Usui A, Kumode M, Iwasa M, Nishimura R, Kawahara M, Minamiguchi H, Kito K, Andoh A
Organizer
第79回日本血液学会学術集会
Related Report
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