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Analysis of GATA4 dimarization during hypertrophic responses

Research Project

Project/Area Number 15K21279
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Biological pharmacy
Cardiovascular medicine
Research InstitutionUniversity of Shizuoka

Principal Investigator

SUNAGAWA YOICHI  静岡県立大学, 薬学部, 助教 (30466297)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
KeywordsGATA4 / 心肥大反応 / 二量体形成 / 二量体化 / 結晶構造解析 / 転写因子 / 心肥大 / p300 / 二量体
Outline of Final Research Achievements

A zinc finger protein, GATA4, associates with an intrinsic histone acetyltransferase (HAT), p300, and regulates myocardial transcriptional activities in response to hypertrophic stimuli. In this study, we demonstrated whether GATA4 formed a homo-dimer and its functional mechanism. Chemical cross-linking assay using nuclear extract from HEK293T cells showed that GATA4 homo-dimer was increased by co-expression of p300. IP-WB assay demonstrated that co-expression of GATA4 with p300 increased the formation of its homo-dimer as well as its acetylation. HAT-deficient mutant of p300 and acetyl-deficient mutant of GATA4 did not increase this homo-dimerization as well as GATA4-acetylation. These results suggest that acetylation of GATA4 is required for the formation of GATA4 dimerization. Thus, this dimerization may regulate hypertrophy-response gene activations and the development of heart failure.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (17 results)

All 2018 2017 2016 2015

All Presentation (17 results) (of which Int'l Joint Research: 5 results)

  • [Presentation] Determination and crystallization of GATA4 dimerization domain spectrometry.2018

    • Author(s)
      Shimizu S, Hara K, Sunagawa Y, Hishiki A, Miyazaki Y, Katanasaka Y, Funamoto M, Sari N, Shimizu K, Wada H, Hasegawa K, Hashimoto H, Morimoto T.
    • Organizer
      IUBMB Focused Meeting on GATA Transcription Factors,
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The Dimerization of GATA4 is Involved in Hypertrophic Responses in Cardiomyocytes2018

    • Author(s)
      ○Shimizu S, Yorimitsu N, Sunagawa Y, Katanasaka Y, Miyazaki Y, Funamoto M, Wada H, Hasegawa K, Morimoto T
    • Organizer
      Asian Pacific Society of Cardiology Congress 2018
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Dimerization domain of GATA4, a hypertrophy-responsive transcription factor is the therapeutic targets2018

    • Author(s)
      Shimizu S., Hara K, Sunagawa Y, Hishiki A, Funamoto M, Miyazaki Y, Katanasaka Y, Wada H, Hasegawa K, Hashimoto H, Morimoto T
    • Organizer
      第1回日本循環器学会基礎研究フォーラム
    • Related Report
      2017 Annual Research Report
  • [Presentation] 心肥大応答を司る転写因子GATA4の二量体形成・DNA結合部位の同定と結晶化2018

    • Author(s)
      清水聡史, 原幸大, 砂川陽一, 菱木麻美, 宮崎雄輔, 刀坂泰史, 船本雅文, Nurmila Sari, 清水果奈, 和田啓道, 長 谷川浩二, 橋本博, 森本達也
    • Organizer
      日本 薬学会第138年会,
    • Related Report
      2017 Annual Research Report
  • [Presentation] The dimerization domain of the hypertrophy-responsive transcription factor GATA4 is a therapeutic target for heart failure2018

    • Author(s)
      Shimizu S., Hara K, Sunagawa Y, Hishiki A, Funamoto M, Miyazaki Y, Katanasaka Y, Wada H, Hasegawa K, Hashimoto H, Morimoto T
    • Organizer
      第82回日本循環器学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 心肥大反応に関わるGATA4のZF部位のX線結晶構造解析2017

    • Author(s)
      清水聡史、原幸大、砂川陽一、刀坂泰史、和田啓道、長谷川浩二、森本達也
    • Organizer
      日本薬学会第137回年会
    • Place of Presentation
      東北大学 他
    • Year and Date
      2017-03-24
    • Related Report
      2016 Research-status Report
  • [Presentation] The dimerization domain of GATA4 is involved in the activation of hypertrophic response2017

    • Author(s)
      Satoshi Shimizu, Natsumi Yorimitsu, Yoichi Sunagawa, Masafumi Funamoto, Yasufumi Katanasaka, Hiromichi Wada, Koji Hasegawa, Tatsuya Morimoto
    • Organizer
      第81回日本循環器学会学術集会
    • Place of Presentation
      石川県立音楽堂 他
    • Year and Date
      2017-03-17
    • Related Report
      2016 Research-status Report
  • [Presentation] 心不全に関わる転写因子GATA4の結晶構造解析2017

    • Author(s)
      清水聡史、原幸大、砂川陽一、刀坂泰史、和田啓道、長谷川浩二、橋本博、森本達也
    • Organizer
      量子ビームサイエンスフェスタ
    • Place of Presentation
      つくば国際会議場
    • Year and Date
      2017-03-14
    • Related Report
      2016 Research-status Report
  • [Presentation] Homo-dimerization of GATA4 is formed through C-terminal zinc finger domain2016

    • Author(s)
      Satoshi Shimizu, Natsumi Yorimitsu, Yoichi Sunagawa, Masafumi Funamoto, Yasufumi Katanasaka, Hiromichi Wada, Koji Hasegawa, Tatsuya Morimoto
    • Organizer
      International Society of Cardiomyopathies and Heart Failure 2016
    • Place of Presentation
      京都国際会館
    • Year and Date
      2016-12-02
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Acetylated form of GATA4 is required for GATA4 homo-dimerization2016

    • Author(s)
      Satoshi Shimizu, Natsumi Yorimitsu, Yoichi Sunagawa, Masafumi Funamoto, Yasufumi Katanasaka, Hiromichi Wada, Koji Hasegawa, Tatsuya Morimoto
    • Organizer
      第21回静岡健康長寿学術フォーラム
    • Place of Presentation
      グランシップ静岡
    • Year and Date
      2016-11-25
    • Related Report
      2016 Research-status Report
  • [Presentation] Homo-dimarization domain of GATA4 involved in p300/GATA4-dependent hypertrophic gene activations2016

    • Author(s)
      Natsumi Yorimitsu, Satoshi Shimizu, Yoichi Sunagawa, Masafumi Funamoto, Yasufumi Katanasaka, Hiromichi Wada, Koji Hasegawa, Tatsuya Morimoto
    • Organizer
      第21回静岡健康長寿学術フォーラム
    • Place of Presentation
      グランシップ静岡
    • Year and Date
      2016-11-25
    • Related Report
      2016 Research-status Report
  • [Presentation] Overexpression of GATA4 dimerization domain inhibited p300/GATA4-dependent hypertrophic genes transcription2016

    • Author(s)
      Natsumi Yorimitsu, Satoshi Shimizu, Yoichi Sunagawa, Masafumi Funamoto, Yasufumi Katanasaka, Hiromichi Wada, Koji Hasegawa, Tatsuya Morimoto
    • Organizer
      The 3rd International Conference on Pharma-Food (ICPF 2016)
    • Place of Presentation
      日本平ホテル
    • Year and Date
      2016-11-17
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Acetylation of GATA4 is required for the formation of GATA4 Homo-dimerization2016

    • Author(s)
      Satoshi Shimizu, Natsumi Yorimitsu, Yoichi Sunagawa, Masafumi Funamoto, Yasufumi Katanasaka, Hiromichi Wada, Koji Hasegawa, Tatsuya Morimoto
    • Organizer
      The 3rd International Conference on Pharma-Food (ICPF 2016)
    • Place of Presentation
      日本平ホテル
    • Year and Date
      2016-11-17
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 心筋細胞肥大に関与する転写因子GATA4はZincフィンガードメインで直接結合し、ホモ二量体を形成する2016

    • Author(s)
      清水聡史、依光奈津美、砂川陽一、刀坂泰史、和田啓道、長谷川浩二、橋本博、森本達也
    • Organizer
      日本病院薬剤師会東海ブロック 日本薬学会東海支部 合同学術大会2017
    • Place of Presentation
      阿波観光ホテル
    • Year and Date
      2016-06-25
    • Related Report
      2016 Research-status Report
  • [Presentation] 心肥大反応を司る転写因子GATA4の二量体はC末のZFドメインで形成される2016

    • Author(s)
      依光奈津美、清水聡史、砂川陽一、刀坂泰史、和田啓道、長谷川浩二、橋本博、森本達也
    • Organizer
      日本病院薬剤師会東海ブロック 日本薬学会東海支部 合同学術大会2017
    • Place of Presentation
      長良川国際会議場
    • Related Report
      2016 Research-status Report
  • [Presentation] 心臓特異的転写因子GATA4の二量体化部位の同定とアセチル化の意義の解明2015

    • Author(s)
      依光奈津美、 砂川陽一、羽鹿成人、刀坂泰史、和田啓道、島津章、長谷川浩二、森本達也
    • Organizer
      日本病院薬剤師会東海ブロック・日本薬学会東海支部 合同学術大会2015
    • Place of Presentation
      愛知
    • Year and Date
      2015-11-01
    • Related Report
      2015 Research-status Report
  • [Presentation] 心臓特異的転写因子GATA4の二量体化部位の同定とアセチル化の意義について2015

    • Author(s)
      依光奈津美、 砂川陽一、羽鹿成人、刀坂泰史、和田啓道、島津章、長谷川浩二、森本達也
    • Organizer
      第1回J-ISCP学術集会
    • Place of Presentation
      京都
    • Year and Date
      2015-06-20
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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