2020 Fiscal Year Final Research Report
Elucidation of epigenetic regulation of erythropoiesis and translation to therapeutic strategy
Project/Area Number |
20K20382
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Project/Area Number (Other) |
18H05374 (2018-2019)
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Research Category |
Grant-in-Aid for Challenging Research (Pioneering)
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Allocation Type | Multi-year Fund (2020) Single-year Grants (2018-2019) |
Review Section |
Medium-sized Section 48:Biomedical structure and function and related fields
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Research Institution | Tohoku University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
張替 秀郎 東北大学, 医学系研究科, 教授 (50302146)
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Project Period (FY) |
2018-06-29 – 2021-03-31
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Keywords | 造血幹細胞 / 老化 / 転写因子 / 遺伝子発現 / 骨髄異形成症候群 |
Outline of Final Research Achievements |
We aimed to understand the roles of MAT2, which synthesizes S-adenosylmethionine (SAM), in red blood cell (RBC) development including the effect of SAM in their epigenome. We found that the expression of MAT2A, the catalytic subunit of MAT2, is gradually decreased along RBD differentiation with concomitant decrease in SAM. The reduction of SAM led to global alterations in the epigenome of precursor cells (erythroid cells) including DNA methylation and histone methylation. As MAT2A expression is maintained by a feedback regulation involving SAM in other types of cells like Hela cells, our results suggest that erythroid cells lack the feedback regulation, enabling them to use the reduction of SAM as a signal to drive RBC differentiation.
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Free Research Field |
医歯薬学
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Academic Significance and Societal Importance of the Research Achievements |
赤血球は酸素運搬を担う細胞であり、体を構成する約30兆個の細胞の実に8割を占める。その寿命は約4ヶ月であり、日々大量の赤血球が骨髄で作り出される。この赤血球造血過程は鉄不足、遺伝的異常、感染症、加齢などによりしばしば障害され、貧血を引き起こす。貧血は世界で罹患者数が最も多い疾患の一つであるが、その根本的治療法の選択肢は十分とは言えない。本研究によりMAT2が貧血治療薬の標的となることが示唆された。
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