| Project/Area Number |
17K18196
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Functional basic dentistry
Morphological basic dentistry
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| Research Institution | Tsurumi University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | G9a / Runx2 / 骨芽細胞分化 / osteogenic front / Senescence / 細胞増殖 / ヒストンメチル化 / エピジェネティクス |
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| Outline of Final Research Achievements |
In this study, we aimed to elucidate how histone methyltransferase G9a integrally regulates the expression of proliferation-related genes in osteoblast progenitors at the osteogenic front. We found that the expression of Runx2 was not altered, but the expression of Runx2-regulated Fgfrs (proliferation-related genes) and Osteocalcin (differentiation marker genes) was repressed in G9a-deficient cells. Both G9a and Runx2 bound to the transcriptional regulatory regions of Fgfrs and Osteocalcin, and endogenous G9a bound to Runx2, indicating that G9a enhanced the transcriptional activation of Runx2.
These results suggest that G9a may be a member of the transcriptional regulatory complex of Runx2, which regulates transcription of genes involved in proliferation and differentiation of progenitor osteoblasts.
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| Academic Significance and Societal Importance of the Research Achievements |
ヒストンメチル化酵素G9aは元来、ヒストン H3、9番目リジン残基(H3K9)のモノメチル化(me1)とジメチル化(me2)を担うヒストン修飾酵素として同定された。さらにヒストン以外の機能性タンパク質のメチル化を担う事も報告されてきた。本研究では、G9aがRunx2による転写複合体に含まれており機能的な役割を担う、ヒストン修飾酵素以外の新たな点が示唆された。
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