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Investigation of the transcriptional coregulator involved in crosstalk between histone acetylation and methylation

Research Project

Project/Area Number 16K15216
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field General medical chemistry
Research InstitutionShiga University of Medical Science

Principal Investigator

Nishi Eiichiro  滋賀医科大学, 医学部, 教授 (30362528)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords転写コレギュレーター / ヒストン修飾 / 細胞周期 / 生体分子
Outline of Final Research Achievements

Nardilysin (NRDC) is a metalloendopeptidase of the M16 family and activates ectodomain cleavage of membrane proteins on the cell surface. On the other hand, nuclear NRDC specifically binds to H3K4me2 and controls transcriptional regulation. Analysis of genetically-modified mice revealed that NRDC play important roles in cancer, inflammation and energy metabolism. In the present study, we combined high-throughput chromatin immunoprecipitation-sequencing and RNA-sequencing analyses to achieve the first genome-wide identification of NRDC target genes in immortalized mouse embryo fibroblasts. We found that global H3K9ac and H3K4me2 levels at NRDC-binding promoters were controled and that a set of genes integral to cell cycle maintenance was directly activated by NRDC. Collectively, these results suggest that the NRDC-mediated epigenetic regulation of cell cycle-associated genes is a fundamental component of the biological functions of NRDC.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report

Research Products

(28 results)

All 2018 2017 2016 Other

All Journal Article (10 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 10 results,  Open Access: 7 results,  Acknowledgement Compliant: 3 results) Presentation (15 results) (of which Int'l Joint Research: 3 results,  Invited: 4 results) Remarks (2 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Nardilysin controls intestinal tumorigenesis through HDAC1/p53-dependent transcriptional regulation.2018

    • Author(s)
      Kanda K, Sakamoto J, Matsumoto Y, Ikuta K, Goto N, Morita Y, Ohno M, Nishi K, Eto K, Kimura Y, Nakanishi Y, Ikegami K, Yoshikawa T, Fukuda A, Kawada K, Sakai Y, Ito A, Yoshida M, Kimura T, Chiba T, Nishi E, Seno H.
    • Journal Title

      JCI insight

      Volume: 3 Issue: 8 Pages: 1-15

    • DOI

      10.1172/jci.insight.91316

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Nardilysin promotes hepatocellular carcinoma through activation of signal transducer and activator of transcription 32017

    • Author(s)
      Kasai Y, Toriguchi K, *Hatano E, Nishi K, Ohno M, Yoh T, Fukuyaman K, Nishio T, Okuno M, Iwaisako K, Seo S, Taura K, Kurokawa M, Kunichika M, Uemoto S, *Nishi E
    • Journal Title

      Cancer Sci

      Volume: 108 Pages: 910-17

    • DOI

      10.1111/cas.13204

    • NAID

      120006333898

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Nardilysin is a promising biomarker for the early diagnosis of acute coronary syndrome2017

    • Author(s)
      Chen Po-Min、Ohno Mikiko、Hiwasa Takaki、Nishi Kiyoto、Saijo Sayaka、Sakamoto Jiro、Morita Yusuke、Matsuda Shintaro、Watanabe Shin、Kuwabara Yasuhide、Ono Koh、Imai Masao、Inoue Katsumi、Murai Tatsuya、Inada Tsukasa、Tanaka Masaru、Kita Toru、Kimura Takeshi、Nishi Eiichiro
    • Journal Title

      Int J Cardiol.

      Volume: 243 Pages: 1-8

    • DOI

      10.1016/j.ijcard.2017.04.047

    • NAID

      130007900462

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nardilysin is involved in autoimmune arthritis via the regulation of tumour necrosis factor alpha secretion2017

    • Author(s)
      Fujii Takayuki、Nishi Eiichiro、Ito Hiromu、Yoshitomi Hiroyuki、Furu Moritoshi、Okabe Namiko、Ohno Mikiko、Nishi Kiyoto、Morita Yusuke、Morita Yugo、Azukizawa Masayuki、Okahata Akinori、Tomizawa Takuya、Kimura Takeshi、Matsuda Shuichi
    • Journal Title

      RMD Open.

      Volume: 3

    • DOI

      10.1136/rmdopen-2017-000436

    • NAID

      120006325113

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genome-wide profiling of nardilysin target genes reveals its role in epigenetic regulation and cell cycle progression2017

    • Author(s)
      Morita Y, Ohno M, Nishi K, Hiraoka Y, Saijo S, Matsuda S, Kita T, Kimura T, Nishi E.
    • Journal Title

      Scientific Reports

      Volume: 7 Pages: 14801-14801

    • DOI

      10.1038/s41598-017-14942-4

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Association of serum levels of antibodies against MMP1, CBX1, and CBX5 with transient ischemic attack and cerebral infarction2017

    • Author(s)
      Wang H,Zhang X-M,Tomiyoshi G,Nakamura R,Shinmen N,Kuroda H,Kimura R,Mine S,Kamitsukasa I,Wada T,Aotsuka A,Yoshida Y,Kobayashi E,Matsutani T,Iwadate Y,Sugimoto K,Mori M,Uzawa A,Muto M,Kuwabara S,Takemoto M,Kobayashi K,Kawamura H,Ishibashi R,Yokote K,Ohno M,
    • Journal Title

      Oncotarget

      Volume: 9 Pages: 5600-5613

    • DOI

      10.18632/oncotarget.23789

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Elevation of autoantibody level against PDCD11 in patients with transient ischemic attack2017

    • Author(s)
      Yoshida Y、Wang H、Hiwasa T、Machida T、Kobayashi E、Mine S、Tomiyoshi G、Nakamura R、Shinmen N、Kuroda H、Takizawa H、Kashiwado K、Kamitsukasa I、Shin H、Wada T、Aotsuka A、Nishi E、Ohno M、Takemoto M、Yokote K、Takahashi S、Matsushima J、Zhang Xiao-Meng、Takiguchi M、Iwadate Y
    • Journal Title

      Oncotarget

      Volume: 9 Pages: 8836-8848

    • DOI

      10.18632/oncotarget.23653

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Loss of Nardilysin, a mitochondrial co-chaperone for α-Ketoglutarate Dehydrogenase, promotes mTORC1 activation and neurodegeneration.2017

    • Author(s)
      Yoon W.H., Sandoval H.,Nagarkar-Jaiswal S.,Jaiswal M.,Yamamoto S., Haelterman N.A., Putluri N., Putluri V., Sreekumar A., Tos T., Aksoy A., Donti T., Graham B.H., Ohno M., Nishi E., Hunter J., Muzny D.M.,Carmichael J.,Shen J.,Arboleda V.A.,Nelson S.F.,Wangler M.F.,Karaca E.,Lupski J.R.,Bellen H.
    • Journal Title

      Neuron

      Volume: 93 Pages: 115-131

    • DOI

      10.1016/j.neuron.2016.11.038

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Nardilysin regulates inflammation, metaplasia, and tumors in murine stomach2017

    • Author(s)
      Kimura Y, Ikuta K, Kimura T, Chiba T, Oshima H, Oshima M, *Nishi E, *Seno H
    • Journal Title

      Scientific Reports

      Volume: 7 Pages: 43052-43052

    • DOI

      10.1038/srep43052

    • NAID

      120006355734

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Nardilysin is required for maintaining pancreatic β-Cell Function.2016

    • Author(s)
      Nishi K, Sato Y, Ohno M, Hiraoka Y, Saijo S, Sakamoto J, Chen P-M, Morita Y, Matsuda S, Iwasaki K, Sugizaki K, Harada N, Mukumoto Y, Kiyonari H, Furuyama K, Kawaguchi Y, Uemoto S, Kita T, Inagaki N, Kimura T and Nishi E
    • Journal Title

      Diabetes.

      Volume: 65 Pages: 3015-27

    • DOI

      10.2337/db16-0178

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Nardilysin Critically Regulates Insulin Secretion and Glucose Metabolism2017

    • Author(s)
      Nishi K, Ohno M, Saijo S, Morita Y, Matsuda S, Sakamoto J, Chen P, Kimura T, Nishi E
    • Organizer
      第81回日本循環器学会学術集会
    • Place of Presentation
      金沢
    • Year and Date
      2017-03-17
    • Related Report
      2016 Research-status Report
  • [Presentation] 多機能ペプチダーゼによる心臓交感神経分布と循環動態の制御2017

    • Author(s)
      西 英一郎
    • Organizer
      第38回日本循環制御医学会総会・学術総会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] ナルディライジンによるp75NTRシェディングを介する心臓交感神経分布パターンの決定2017

    • Author(s)
      西 英一郎、大野 美紀子
    • Organizer
      第40回日本神経科学大会 NEUROSCIENCE2017
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 急性冠症候群における新規バイオマーカー「ナルディライジン」の有用性についての検討2017

    • Author(s)
      大野美紀子、陳博俊、日和佐隆樹、西清人、西城さやか、森田雄介、松田真太郎、木村剛、西英一郎
    • Organizer
      第22回日本病態プロテアーゼ学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ゲノムワイド統合解析によるナルディライジンの細胞周期制御機構の解明2017

    • Author(s)
      森田雄介, 大野美紀子, 西清人, 西城さやか, 松田真太郎, 木村剛, 西英一郎
    • Organizer
      第22回日本病態プロテアーゼ学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 脂肪組織のナルディライジンはインスリン感受性を制御する2017

    • Author(s)
      松田真太郎, 森田雄介, 岩﨑広高, 大野美紀子, 木村剛, 西英一郎
    • Organizer
      Molecular Cardiovascular Metabolic Conference 2017
    • Related Report
      2017 Annual Research Report
  • [Presentation] ナルディライジンは神経栄養因子受容体(p75NTR)のシェディングを介して心臓交感神経の分布を制御する2017

    • Author(s)
      大野美紀子, 西 清人, 平岡 義範, 新妻 晋一郎, 西城 さやか, 坂本 二郎, 陳 博俊, 森田 雄介, 松田 真太郎, 椋本 淑子, 清成 寛, 松浦 博, 北 徹, 木村 剛, 西 英一郎.
    • Organizer
      生命科学系学会合同年次大会(第40回日本分子生物学会年会)
    • Related Report
      2017 Annual Research Report
  • [Presentation] Nardilysin-mediated epigenetic regulation contributes to the cell cycle progression and proliferation in mouse embryonic fibroblasts2017

    • Author(s)
      森田雄介, 大野美紀子, 西清人, 西城さやか, 松田真太郎, 木村剛, 西英一郎
    • Organizer
      生命科学系学会合同年次大会(第40回日本分子生物学会年会)
    • Related Report
      2017 Annual Research Report
  • [Presentation] 脂肪細胞のナルディライジンはインスリン感受性および脂肪組織の慢性炎症を制御する2017

    • Author(s)
      松田真太郎, 森田雄介, 岩﨑広高, 大野美紀子, 木村剛, 西英一郎
    • Organizer
      生命科学系学会合同年次大会(第40回日本分子生物学会年会)
    • Related Report
      2017 Annual Research Report
  • [Presentation] MicroRNA-494は転写共役因子p300を介して筋線維型特異的ヒト骨格筋細胞分化を制御する2017

    • Author(s)
      岩﨑広高、今村武史、森野勝太郎、櫻井英俊、大野美紀子、前川聡、西英一郎
    • Organizer
      生命科学系学会合同年次大会(第40回日本分子生物学会年会)
    • Related Report
      2017 Annual Research Report
  • [Presentation] ナルディライジンによるPER2の機能調節を介した概日リズム制御機構2017

    • Author(s)
      平岡義範、吉種光、大野美紀子, 森田雄介、布川莉奈、西清人、久米典昭、木村剛、深田吉孝、西英一郎
    • Organizer
      生命科学系学会合同年次大会(第40回日本分子生物学会年会)
    • Related Report
      2017 Annual Research Report
  • [Presentation] Nardilysin is a Promising Biomarker for the Early Diagnosis of Acute Coronary Syndrome.2016

    • Author(s)
      Ohno M, Chen P-M, Hiwasa T, Nishi K, Saijo S, Sakamoto J, Morita Y, Watanabe S, Kuwabara Y, Ono K, Imai M, Inoue K, Murai T, Kita T, Kimura T, and Nishi E.
    • Organizer
      American Heart Association Scientific Session
    • Place of Presentation
      New Orleans, LA
    • Year and Date
      2016-11-12
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Nardilysin regulates intestinal tumor development through its multifaceted functions2016

    • Author(s)
      Nishi E
    • Organizer
      The 14th Matsuyama International Symposium on Proteo-Sciences
    • Place of Presentation
      Matsuyama
    • Year and Date
      2016-09-16
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Nardilysin, a novel biomarker for hepatocellular carcinoma, enhances diethylnitrosamine-induced mice carcinogenesis and cancer cell proliferation via activation of STAT3 signaling pathway2016

    • Author(s)
      Kasai Y, Hatano E, Nishi E, Toriguchi K, Yoh T, Nishio T, Okuno M, Seo S, Taura K, Yasuchika K, Okajima H, Kaido T, Uemoto S
    • Organizer
      International Liver Cancer Association 2016
    • Place of Presentation
      Vancouber
    • Year and Date
      2016-09-09
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Critical roles of nardilysin in energy metabolism2016

    • Author(s)
      西 英一郎
    • Organizer
      第21回アディポサイエンスシンポジウム
    • Place of Presentation
      大阪
    • Year and Date
      2016-08-20
    • Related Report
      2016 Research-status Report
    • Invited
  • [Remarks] 滋賀医科大学 薬理学講座 ホームページ

    • URL

      http://www.shiga-med.ac.jp/pharm/

    • Related Report
      2017 Annual Research Report
  • [Remarks] 滋賀医科大学 薬理学講座 ホームページ

    • URL

      http://www.shiga-med.ac.jp/pharm/index.html

    • Related Report
      2016 Research-status Report
  • [Patent(Industrial Property Rights)] 検査方法及び肝内胆管がん用検査試薬2017

    • Inventor(s)
      西 英一郎、大野 美紀子、黒川 祐人、山口 里奈
    • Industrial Property Rights Holder
      西 英一郎、大野 美紀子、黒川 祐人、山口 里奈
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2017-022201
    • Filing Date
      2017-02-09
    • Related Report
      2016 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2019-03-29  

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