2021 Fiscal Year Final Research Report
LncRNA connecting H3K27 demethylation with signal transduction cancer controls cell fate regulation.
| Project/Area Number |
19H03501
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 50010:Tumor biology-related
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 長鎖ノンコーディングRNA / エピゲノム因子 / 転写制御 |
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| Outline of Final Research Achievements |
We found ELIT-1 as a novel llncRNA induced by TGFβ and involved in epithelial-mesenchymal transition (EMT). ELIT-1 is transcriptionally induced via the TGFβ-Smad pathway. ELIT-1 binds to Smad, promotes transcription of EMT-related genes such as Snail and N-cadherin, and positively regulates EMT. Furthermore, this study demonstrated that ELIT-1 binds to an H3K27 demethylase (referred to as KDM-X). It was suggested that ELIT-1 promotes H3K27 demethylation of the target gene by promoting the recruitment of KDM-X to the promoter of the target gene in a Smad3-dependent manner, and participates in gene expression.
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| Free Research Field |
分子生物学
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| Academic Significance and Societal Importance of the Research Achievements |
これまでの研究で、ヒストン脱メチル化を含むエピゲノム修飾によるクロマチン構造制御が遺伝子の発現制御に極めて重要であることは周知の事実である。しかしながらエピゲノム因子はDNA結合能を持たず、どのようなメカニズムで遺伝子特異的なエピゲノム修飾を実行するのかは不明な点が多かった。本研究により、lncRNAが転写因子とエピゲノム因子と結合して、転写因子依存的に標的遺伝子のプロモーターへエピゲノム因子を運ぶ機能をしていることが示唆された。
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