| Project/Area Number |
16K09902
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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 |
Collagenous pathology/Allergology
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| Research Institution | Saitama Medical University |
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Principal Investigator |
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| Research Collaborator |
KUROKAWA riki
NOMA hisashi
ARAKI yasuto
KUROSAWA natsuko
AIZAKI yoshimi
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | エピジェネティクス / ヒストンメチル化 / エピジェティクス / 成人スティル病 / ヒストン修飾 / エピゲノム / 内科 / 免疫学 / 末梢血 |
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| Outline of Final Research Achievements |
1) Histone modification in peripheral blood nucleated cells from adult-onset Still's disease (AOSD) was detected by flow cytometric analysis using specific antibodies against H3K4me3 or H3K27me3. There were specific aberrations of histone methylation in monocytes, neutrophils and B cells from AOSD patients comparing with healthy controls or other disease controls. Of interest was these histone methylation abnormalities were significantly associated with disease activity. Additionally aberrant histone methylations of a specific subset of monocyte with CD14++CD16- were significantly correlated with serum IL-18 concentration.
2) To analyze the pathogenic mechanism of AOSD from epigenetic point of view, ATAC-Seq was performed to identify genes with open chromatins. However, the technique showed nothing and an alternative method was carried out. We made transcriptome analysis and found several candidates of the target genes. We now preparing for ChIP-Seq analysis for the purpose above.
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| Academic Significance and Societal Importance of the Research Achievements |
この研究においては、病気の原因の不明な成人発症スチル病（AOSD）の原因を解明するために、血液中の白血球のエピゲノム異常（遺伝子に変化を認めないけれどタンパク質の発現には変化が見られる制御機構）、特にヒストン修飾変化を各細胞亜群毎に解明する研究で、私達は単球という細胞群においてヒストンのメチル化異常を認めた。さらに、このメチル化異常の結果、どのような遺伝子の発現に変化が見られるのかを明らかにした。それを基に、この結果が蛋白の発現に影響するのか、そしてどのように病気の状態に関与するのか現在も研究を進めています。これが明らかになれば、新規治療法の開発に繋がる。
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