Functional Analyses of epigenetic molecules associated with early induced transcription factors in angiogenesis
| Project/Area Number |
17H03614
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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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| Research Field |
Medical genome science
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| Research Institution | The University of Tokyo |
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Principal Investigator |
KANKI YASUHARU 東京大学, アイソトープ総合センター, 助教 (00534869)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2019: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2017: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
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| Keywords | 血管新生 / エピジェネティクス / VEGF / 疾患エピジェネティクス / ヒストン修飾 / 疾患エピゲノミクス / 血管生物学 / 立体構造解析 / 構造生物学 / クライオ電子顕微鏡 |
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| Outline of Final Research Achievements |
This study was initiated with the aim of identifying candidate molecules of new drugs that do not inhibit physiological angiogenesis but inhibit pathological angiogenesis involved in malignant solid tumor growth and progression. Based on multi-omics analysis of human vascular endothelial cells stimulated with vascular endothelial growth factor (VEGF), we identified two epigenomic modification-related molecules, PTIP and PCGF3, as candidate targets. Next, we generated vascular endothelial cell-specific Pcgf3 knockout mice, which resulted in the inhibition of angiogenesis. This study not only identified the first epigenome-associated factor in angiogenesis, but its inhibition also resulted in reduction of angiogenesis in vivo, making it a promising candidate for future anti-angiogenic drugs.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究成果により、遺伝子の一過性の転写に抑制系タンパク質複合体PRC1.3の関与があるという従来にない機構を示すことができ、この点において学術的意義の高い研究となった。一方で、生理的な血管新生を阻害せずに、病的血管新生を阻害する候補となるエピゲノム関連因子を同定した。現在、臨床では抗血管新生阻害薬は抗がん剤のみならず、糖尿病性網膜症、加齢黄斑変性症など、多岐にわたる。悪性腫瘍や生活習慣病悪化によるQOLの低下が、医療経済の圧迫の要因の一つであることを鑑みると、本研究成果を生かした創薬は、わが国だけではなく、他の先進国でもインパクトのある結果となる。
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Report
(4 results)
Research Products
(33 results)
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[Journal Article] Coordinated demethylation of H3K9 and H3K27 is required for rapid inflammatory responses of endothelial cells2020
Author(s)
Higashijima Y, Matsui Y, Shimamura T, Nakaki R, Nagai N, Tsutsumi S, Abe Y, Link VM, Osaka M, Yoshida M, Watanabe R, Tanaka T, Taguchi A, Miura M, Ruan X, Li G, Inoue T, Nangaku M, Kimura H, Furukawa T, Aburatani H, Wada Y, Ruan Y, Glass CK, Kanki Y
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Journal Title
The EMBO Journal
Volume: 39
Issue: 7
Pages: 1-1
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Comprehensive epigenome characterization reveals diverse transcriptional regulation across human vascular endothelial cells2019
Author(s)
Nakato R, Wada Y, Nakaki R, Nagae G, Katou Y, Tsutsumi S, Nakajima N, Fukuhara H, Iguchi A, Kohro T, Kanki Y, Saito Y, Kobayashi M, Izumi-Taguchi A, Osato N, Tatsuno K, Kamio A, Hayashi-Takanaka Y, Wada H, Ohta S, Aikawa M, Nakajima H, Nakamura M, McGee RC, Heppner KW, Kawakatsu T, Genno M, Yanase H, Kume H, et al.
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Journal Title
Epigenetics & Chromatin
Volume: 12
Issue: 1
Pages: 77-77
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Phosphoethanolamine Accumulation Protects Cancer Cells under Glutamine Starvation through Downregulation of PCYT22019
Author(s)
Osawa T, Shimamura T, Saito K, Hasegawa Y, Ishii N, Nishida M, Ando R, Kondo A, Anwar M, Kato K, Endo K, Yamano S, Kanki Y, Matsumura Y, Minami T, Tanaka T, Anai M, Wada Y, Wanibuchi H, Hayashi M, Hamada A, Yoshida M, Yachida S, Nakao M, Sakai J, Aburatani H, Shibuya M, Hanada K, Miyano S, Soga T, Kodama T
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Journal Title
Cell Rep.
Volume: 29(1)
Issue: 1
Pages: 89-103
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Coordinated demethylation of H3K9 and H3K27 is required for rapid inflammatory responses of endothelial cells2018
Author(s)
Higashijima Y, Matsui Y, Shimamura T, Tsutsumi S, Nakaki R, Abe Y, Link VM, Osaka M, Yoshida M, Watanabe R, Tanaka T, Taguchi A, Miura M, Inoue T, Nangaku M, Kimura H, Furukawa T, Aburatani H, Wada Y, Glass CK, Kanki Y
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Journal Title
bioRxiv
Volume: -
Pages: 456491-456491
DOI
NAID
Related Report
Open Access / Int'l Joint Research
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[Journal Article] Dynamically and epigenetically coordinated GATA/ETS/SOX transcription is indispensable for endothelial cell differentiation2017
Author(s)
Kanki Y, Nakaki R, Shimamura T, Matsunaga T, Yamamizu K, Katayama S, Suehiro JI, Osawa T, Aburatani H, Kodama T, Wada Y, Yamashita JK, Minami T.
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Journal Title
Nucleic Acids Research
Volume: 印刷中
Issue: 8
Pages: 4344-4358
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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