2018 Fiscal Year Final Research Report
Identification and regulation mechanism of enhancers for hematopoietic cell fate decision
| Project/Area Number |
16K09846
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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 |
Hematology
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
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| Research Collaborator |
Tatsumi Goichi
Asai Ai
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | 白血病 / 造血分化 / エンハンサー / ヒストン修飾 |
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| 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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| Free Research Field |
血液腫瘍学
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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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