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Chromatin Dynamics and Epigenetic Regulation of Brown-Fat-Specific Transcription

Research Project

Project/Area Number 25293209
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Metabolomics
Research InstitutionThe University of Tokyo

Principal Investigator

WAKI HIRONORI  東京大学, 医学部附属病院, 特任准教授 (00466765)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000)
Fiscal Year 2015: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2013: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
Keywords褐色脂肪細胞 / 脂肪細胞 / エピゲノム / クロマチン / 遺伝子 / 転写制御 / 分化 / 肥満 / 褐色脂肪 / エンハンサー / 転写因子
Outline of Final Research Achievements

To gain insight into the underlying mechanism of brown fat development, we performed formaldehyde-assisted isolation of regulatory elements analysis coupled with high-throughput sequencing (FAIRE-seq) of murine brown adipose tissue (BAT) and white adipose tissue (WAT). Through motif analysis of BAT-specific open chromatin regions and expression analysis, we identified NFIA as a novel regulator of brown adipocyte differentiation. Using cell culture, NFIA knockout mice, and chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq), we demonstrated that NFIA controls the BAT-specific gene program by activating the cell-type-specific enhancers and facilitating the binding of the adipogenic master regulator, PPARγ.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (27 results)

All 2016 2015 2014 2013

All Journal Article (5 results) Presentation (18 results) (of which Invited: 8 results) Book (4 results)

  • [Journal Article] 肥満関連ゲノム領域とFTO/IRX3の関連と意義2015

    • Author(s)
      青山 倫久, 脇 裕典, 山内 敏正, 門脇 孝
    • Journal Title

      内分泌・糖尿病・代謝内科

      Volume: 40 Pages: 306-311

    • NAID

      40020473774

    • Related Report
      2015 Annual Research Report
  • [Journal Article] エネルギー代謝と遺伝子発現調節(第5回) 脂質代謝調節転写因子PPAR2015

    • Author(s)
      平池 勇雄, 脇 裕典
    • Journal Title

      The Lipid

      Volume: 26 Pages: 403-407

    • Related Report
      2015 Annual Research Report
  • [Journal Article] 褐色細胞組織の機能制御とその破綻2015

    • Author(s)
      脇裕典
    • Journal Title

      医学のあゆみ(第5土曜特集 糖尿病のすべて 基礎研究の最前線)

      Volume: 252(5) Pages: 415-419

    • Related Report
      2014 Annual Research Report
  • [Journal Article] III プロトコール エピゲノム C.クロマチンアクセシビリティ解析 2.オープンクロマチンを同定するFAIRE-seq2014

    • Author(s)
      中村正裕, 脇裕典
    • Journal Title

      実験医学別冊 次世代シークエンス解析スタンダード

      Volume: 0 Pages: 195-203

    • Related Report
      2014 Annual Research Report
  • [Journal Article] エピゲノムと肥満症2014

    • Author(s)
      脇 裕典, 山内 敏正, 門脇 孝
    • Journal Title

      医学のあゆみ (第5土曜特集 肥満の医学 : 臨床と研究の最先端)

      Volume: 250(9) Pages: 797-801

    • Related Report
      2014 Annual Research Report
  • [Presentation] NFIA controls brown fat gene program by colocalizing with PPARγat cell typeat cell type-specific enhancers2016

    • Author(s)
      脇裕典
    • Organizer
      第10回 Cardio-Diabetes研究会
    • Place of Presentation
      東京
    • Year and Date
      2016-03-05
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] NFIAによる細胞特異的エンハンサーのクロマチンリモデリングを介した褐色脂肪遺伝子プログラムの制御2015

    • Author(s)
      脇裕典、平池勇雄、油谷浩幸、山内敏正、門脇孝
    • Organizer
      第38回日本分子生物学会年会第88回日本生化学会大会ワークショップ
    • Place of Presentation
      神戸市
    • Year and Date
      2015-12-02
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] NFIAによる細胞特異的エンハンサーのクロマチンリモデリングを介した褐色脂肪遺伝子プログラムの制御2015

    • Author(s)
      脇裕典、平池勇雄、于静、三宅加奈、中村正裕、鈴木顕、仲木竜、小林博文、孫威、青山倫久、廣田雄輔、冨岡恵、長野学、大野晴也、沖健司、米田真康、堤修一、油谷浩幸、山内敏正、門脇孝
    • Organizer
      第9回Diabetes Leading- edge Conference
    • Place of Presentation
      大津市
    • Year and Date
      2015-08-08
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] シンポジウム4 ゲノム・エピゲノムと糖尿病2015

    • Author(s)
      脇裕典
    • Organizer
      第49回 糖尿病学の進歩 シンポジウム4 ゲノム・エピゲノムと糖尿病
    • Place of Presentation
      岡山市
    • Year and Date
      2015-02-20
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 褐色脂肪特異的な転写制御・エピゲノム制御におけるNFIAの役割の解明2015

    • Author(s)
      脇裕典, 平池勇雄, 于静, 中村正裕, 孫威, 三宅加奈, 鈴木顕, 青山倫久, 冨岡恵, 廣田雄輔, 植木浩二郎, 堤修一, 油谷浩幸, 山内敏正, 門脇孝
    • Organizer
      日本糖尿病・肥満動物学会
    • Place of Presentation
      京都市
    • Year and Date
      2015-02-14
    • Related Report
      2014 Annual Research Report
  • [Presentation] 白色・褐色脂肪細胞におけるクロマチン構造変化とエピゲノム制御の役割2014

    • Author(s)
      脇裕典
    • Organizer
      AdipoScience in Hiroshima
    • Place of Presentation
      広島市
    • Year and Date
      2014-10-31
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Genome-wide Profiling of Brown Fat-Specific Open Regulatory Regions Identifies NFIA as a Transcriptional Regulator of Brown Fat Differentiation2014

    • Author(s)
      Hironori Waki, Yuta Hiraike Jing Yu, Kana Miyake, Masahiro Nakamura, Ken Suzuki, Wei Sun, Megumi Tomioka, Yusuke Hirota, Tomohisa Aoyama, Masato Iwabu, Miki Okada-Iwabu, Kohjiro Ueki, Shuichi Tsutsumi, Hiroyuki Aburatani, Toshimasa Yamauchi and Takashi Kadowaki
    • Organizer
      International Symposium for the Study of Obesity〝Molecular Basis and Disorders of Control of Appetite and Fat Accumulation″
    • Place of Presentation
      Miyazaki, Japan
    • Year and Date
      2014-10-26
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 白色・褐色脂肪細胞におけるクロマチン構造変化とエピゲノム制御の役割2014

    • Author(s)
      脇裕典、平池勇雄、于静、中村正裕、青山倫久、孫威、鈴木顕、若林賢一、井上剛、武和巳、冨岡恵、三宅加奈、廣田雄輔、岩部真人、岩部美紀、杉山拓也、和田洋一郎、植木浩二郎、堤 修一、油谷浩幸、山内敏正、門脇孝
    • Organizer
      第35回日本肥満学会 シンポジウム
    • Place of Presentation
      宮崎市
    • Year and Date
      2014-10-25
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 褐色脂肪分化と遺伝子制御におけるNFIA の役割2014

    • Author(s)
      脇裕典、平池勇雄、于静、中村正裕、鈴木顕、孫威、青山倫久、冨岡恵、杉山拓也、植木浩二郎、堤 修一、油谷浩幸、山内敏正、門脇孝
    • Organizer
      第29回日本糖尿病合併症学会
    • Place of Presentation
      東京
    • Year and Date
      2014-10-03
    • Related Report
      2014 Annual Research Report
  • [Presentation] Genome-wide Profiling of Brown Fat-Specific Open Regulatory Regions Identifies NFIA as a Transcriptional Regulator of Brown Fat Muscle Cell Lineage Specification2014

    • Author(s)
      Hironori Waki, Yuta Hiraike, Jing Yu, Kana Miyake, Masahiro Nakamura, Ken Suzuki, Kohjiro Ueki, Shuichi Tsutsumi, Hiroyuki Aburatani, Toshimasa Yamauchi, Takashi Kadowaki
    • Organizer
      9th Metabolic Syndrome, Type 2 Diabetes and Atherosclerosis Congress
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      2014-09-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] 白色・褐色脂肪細胞におけるクロマチン構造変化とエピゲノム制御の役割2014

    • Author(s)
      脇 裕典
    • Organizer
      第32回内分泌代.謝学サマーセミナー
    • Place of Presentation
      山梨
    • Year and Date
      2014-07-11
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 褐色脂肪細胞特異的な転写制御領域のFAIRE-seqによる新規制御因子の同定2014

    • Author(s)
      脇裕典、平池勇雄、于静、山内敏正、中村正裕、孫威、青山倫久、冨岡恵、岩部真人、岩部美紀、植木浩二郎、堤 修一、油谷浩幸、門脇孝
    • Organizer
      第57回日本糖尿病学会年次学術集会
    • Place of Presentation
      大阪市
    • Year and Date
      2014-05-24
    • Related Report
      2014 Annual Research Report
  • [Presentation] ゲノムワイドFAIRE-seqを用いた褐色脂肪細胞特異的な転写制御機構におけるNFIAの役割の同定2014

    • Author(s)
      脇裕典、平池勇雄、于静、山内敏正、中村正裕、孫威、青山倫久、冨岡恵、岩部真人、岩部美紀、植木浩二郎、堤 修一、油谷浩幸、門脇孝
    • Organizer
      第87回日本内分泌学会学術総会
    • Place of Presentation
      福岡市
    • Year and Date
      2014-04-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] Genome-wide Profiling of Brown Fat-Specific Open Regulatory Regions Identifies NFIA as a Transcriptional Regulator of Brown Fat Muscle Cell Lineage Specification2014

    • Author(s)
      Yuta Hiraike, Jing Yu, Hironori Waki, Masahiro Nakamura, Wei Sun, Tomohisa Aoyama, Megumi Tomioka, Masato Iwabu, Miki Okada-Iwabu, Kohjiro Ueki, Shuichi Tsutsumi, Hiroyuki Aburatani, Toshimasa Yamauchi, Takashi Kadowaki
    • Organizer
      Exploring the Role of Brown Fat in Humans
    • Place of Presentation
      NIH, Bethesda, MD, 米国
    • Related Report
      2013 Annual Research Report
  • [Presentation] Genome-wide Profiling of Brown Fat-Specific Open Regulatory Regions Identifies NFIA as a Transcriptional Regulator of Brown Fat–Muscle Cell Lineage Specification.2013

    • Author(s)
      Hironori Waki
    • Organizer
      Small RNAs to stem Cells & Epigenetics Reprogramming ASIA-2013 Meeting
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] 「シンポジウム3」白色・褐色脂肪細胞におけるクロマチン構造とエピゲノム制御2013

    • Author(s)
      脇 裕典
    • Organizer
      第34回日本肥満学会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] シンポジウム:次世代シークエンサーによるFAIRE-seqを用いた脂肪細胞特異的転写制御領域のゲノムワイド解析2013

    • Author(s)
      脇 裕典
    • Organizer
      第56回日本腎臓学会学術総会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] 褐色脂肪細胞特異的な転写制御領域のFAIRE-seqによる新規制御因子の同定2013

    • Author(s)
      脇裕典、平池勇雄、于静、山内敏正、中村正裕、孫威、青山倫久、冨岡恵、岩部真人、岩部美紀、植木浩二郎、堤 修一、油谷浩幸、門脇孝
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Related Report
      2013 Annual Research Report
  • [Book] 糖尿病学2015

    • Author(s)
      脇 裕典 門脇孝/荒木栄一/稲垣暢也/羽田勝計/綿田裕孝 編集
    • Total Pages
      636
    • Publisher
      西村書店
    • Related Report
      2015 Annual Research Report
  • [Book] 学会誌「糖尿病」特集:糖尿病と遺伝子 4.糖尿病とエピゲノム2014

    • Author(s)
      脇裕典, 山内敏正, 門脇孝
    • Total Pages
      3
    • Publisher
      日本糖尿病学会
    • Related Report
      2013 Annual Research Report
  • [Book] 細胞工学:32 号:明らかになる褐色脂肪組織の機能:今,第三の細胞が目覚め ヒト褐色脂肪細胞の細胞系譜 古典的褐色脂肪細胞か,ベージュ/Brite細胞か?2013

    • Author(s)
      脇裕典, 山内敏正, 門脇孝
    • Total Pages
      7
    • Publisher
      学研メディカル秀潤社
    • Related Report
      2013 Annual Research Report
  • [Book] 期待されるチアゾリジン薬(改訂版)PPARγをめぐる基礎研究の進展-エピゲノム解析をはじめとして2013

    • Author(s)
      脇裕典, 山内敏正, 門脇孝
    • Total Pages
      12
    • Publisher
      フジメディカル出版
    • Related Report
      2013 Annual Research Report

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Published: 2013-05-21   Modified: 2019-07-29  

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