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The molecular mechanism for fundamental properties of circadian clock, input, oscillation, and output

Research Project

Project/Area Number 25440041
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Functional biochemistry
Research InstitutionThe University of Tokyo

Principal Investigator

YOSHITANE Hikari  東京大学, 理学(系)研究科(研究院), 助教 (70569920)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsサーカディアンリズム / 体内時計 / ChIP-Seq解析 / RNA-Seq解析 / インタラクトーム解析 / 転写制御 / バイオインフォマティクス / 生物時計 / 時計遺伝子 / CLOCK / BMAL1 / ChIP-Seq / RNA-Seq
Outline of Final Research Achievements

We previously identified CLOCK-binding sites in mouse liver by ChIP-Seq analysis, and in this study a newly developed bioinformatics method, motif centrality analysis of ChIP-Seq (MOCCS), revealed CACGNG, CACGTT, and CATG[T/C]G as functional E-box sequences targeted by CLOCK. We reported Nrf2 and Nfatc2 genes as rhythmic output genes from the E-boxes. Functional D-box sequences targeted by DBP protein were determined by ChIP-Seq analysis. We also identified CaMKII, UBE3A, and USP7 as a protein kinase for CLOCK phosphorylation, an E3 ligase for BMAL1 ubiquitination, and a de-ubiquitination enzyme for CRY ubiquitination, respectively.

Report

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

    (57 results)

All 2016 2015 2014 2013 Other

All Int'l Joint Research (1 results) Journal Article (8 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 8 results,  Open Access: 6 results,  Acknowledgement Compliant: 3 results) Presentation (39 results) (of which Int'l Joint Research: 2 results,  Invited: 3 results) Book (4 results) Remarks (5 results)

  • [Int'l Joint Research] マンチェスター大学(英国)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] The chondrocyte clock gene Bmal1 controls cartilage homeostasis and integrity2016

    • Author(s)
      Michal Dudek, Nicole Gossan, Nan Yang, Hee-Jeong Im, Jayalath PD Ruckshanthi, Hikari Yoshitane, Xin Li, Ding Jin, Ping Wang, Maya Boudiffa, Ilaria Bellantuono, Yoshitaka Fukada, Ray P. Boot-Handford, and Qing-Jun Meng.
    • Journal Title

      The Journal of Clinical Investigation

      Volume: 126 Issue: 1 Pages: 365-376

    • DOI

      10.1172/jci82755

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Cell-based inhibitor screening identifies multiple protein kinases important for circadian clock oscillations2015

    • Author(s)
      Naohiro Kon, Yasunori Sugiyama, Hikari Yoshitane, Isamu Kameshita, Yoshitaka Fukada
    • Journal Title

      Communicative & Integrative Biology

      Volume: 8 Issue: 4 Pages: 1-4

    • DOI

      10.4161/19420889.2014.982405

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] CLOCK-controlled polyphonic regulations of circadian rhythms through canonical and non-canonical E-boxes.2014

    • Author(s)
      Hikari Yoshitane, Haruka Ozaki, Hideki Terajima, Ngoc-Hien Du, Yutaka Suzuki, Taihei Fujimori, Naoki Kosaka, Shigeki Shimba, Sumio Sugano, Toshihisa Takagi, Wataru Iwasaki, and Yoshitaka Fukada.
    • Journal Title

      Molecular and Cellular Biology

      Volume: 34 Issue: 10 Pages: 1776-1787

    • DOI

      10.1128/mcb.01465-13

    • Related Report
      2014 Research-status Report 2013 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The circadian clock regulates the NRF2/ARE-mediated antioxidant defence pathway in the mouse lung.2014

    • Author(s)
      Pekovic-Vaughan V, Gibbs J, Yoshitane H, Yang N, Pathiranage D, Guo B, Sagami A, Taguchi K, Bechtold D, Loudon A, Yamamoto M, Chan J, van der Horst GTJ, Fukada Y, and Meng Q-J.
    • Journal Title

      Genes Dev

      Volume: 28 Issue: 6 Pages: 548-560

    • DOI

      10.1101/gad.237081.113

    • Related Report
      2014 Research-status Report 2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The E3 ubiquitin ligase UBE3A is an integral component of the molecular circadian clock through regulating the BMAL1 transcription factor.2014

    • Author(s)
      Nicole Gossan, Feng Zhang, Baoqiang Guo, Ding Jin, Hikari Yoshitane, Aiyu Yao, Nick Glossop, Yong Q Zhang, Yoshitaka Fukada, Qing-Jun Meng
    • Journal Title

      Nucl. Acids Res.

      Volume: 42 Issue: 9 Pages: 5765-5775

    • DOI

      10.1093/nar/gku225

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] CaMKII is essential for the cellular clock and coupling between morning and evening behavioral rhythms.2014

    • Author(s)
      Kon N, Yoshikawa T, Honma S, Yamagata Y, Yoshitane H, Shimizu K, Sugiyama Y, Hara C, Kameshita I, Honma K, Fukada Y.
    • Journal Title

      Genes Dev

      Volume: 28 Issue: 10 Pages: 1101-1110

    • DOI

      10.1101/gad.237511.114

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The E3 ubiquitin ligase UBE3A is an integral component of the molecular circadian clock through regulating the BMAL1 transcription factor2014

    • Author(s)
      Nicole Gossan et al.
    • Journal Title

      Nucleic Acids Research

      Volume: 未定

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] CaMKII is Essential for Circadian Clockwork and Coupling of Morning and Evening Oscillators.2014

    • Author(s)
      Naohiro Kon et al.
    • Journal Title

      Genes and Development

      Volume: 未定

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 体内時計の出力リズムを担う時計シスエレメントD-boxの探索2016

    • Author(s)
      浅野吉政、吉種光、尾崎遼、鈴木穣、寺嶋秀騎、佐上彩、布川莉奈、岩崎渉、深田吉孝
    • Organizer
      時間生物フォーラム東京2016
    • Place of Presentation
      早稲田大学(新宿区 東京都)
    • Year and Date
      2016-03-16
    • Related Report
      2015 Annual Research Report
  • [Presentation] 体内時計が生み出すA-to-IRNA編集リズムの重要性2016

    • Author(s)
      寺嶋秀騎、吉種光、尾崎遼、鈴木穣、榛葉繁紀、岩崎渉、深田吉孝
    • Organizer
      時間生物フォーラム東京2016
    • Place of Presentation
      早稲田大学(新宿区 東京都)
    • Year and Date
      2016-03-16
    • Related Report
      2015 Annual Research Report
  • [Presentation] 概日時計をリセットする新規の入力シグナル2016

    • Author(s)
      今村聖路、吉種光、深田吉孝
    • Organizer
      時間生物フォーラム東京2016
    • Place of Presentation
      早稲田大学(新宿区 東京都)
    • Year and Date
      2016-03-16
    • Related Report
      2015 Annual Research Report
  • [Presentation] タンパク質量が顕著に変動するDBPの分解制御2016

    • Author(s)
      増田周作、吉種光、布川莉奈、深田吉孝
    • Organizer
      時間生物フォーラム東京2016
    • Place of Presentation
      早稲田大学(新宿区 東京都)
    • Year and Date
      2016-03-16
    • Related Report
      2015 Annual Research Report
  • [Presentation] ユビキチン化を介したCRYタンパク質の安定性の制御機構2016

    • Author(s)
      野辺加織、吉種光、中川智貴、平野有紗、弓本佳苗、中山敬一、深田吉孝
    • Organizer
      時間生物フォーラム東京2016
    • Place of Presentation
      早稲田大学(新宿区 東京都)
    • Year and Date
      2016-03-16
    • Related Report
      2015 Annual Research Report
  • [Presentation] リズミックな A-to-I RNA 編集による体内時計システムの分子制御2015

    • Author(s)
      寺嶋秀騎、吉種光、尾崎遼、鈴木穣、榛葉繁紀、岩崎渉、深田吉孝
    • Organizer
      BMB2015
    • Place of Presentation
      神戸ポートピアホテル(神戸市、兵庫県)
    • Year and Date
      2015-12-04
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 24時間周期を生み出す時計タンパク質CLOCKとBMAL1のリン酸化制御2015

    • Author(s)
      吉種光、金尚宏、今村聖路、佐上彩、深田吉孝
    • Organizer
      BMB2015
    • Place of Presentation
      神戸ポートピアホテル(神戸市、兵庫県)
    • Year and Date
      2015-12-02
    • Related Report
      2015 Annual Research Report
  • [Presentation] 広範な RNA リズムを作り出す A-to-I RNA 編集と時計振動体との機能連関2015

    • Author(s)
      寺嶋秀騎、吉種光、尾崎遼、鈴木穣、榛葉繁紀、岩崎渉、深田吉孝
    • Organizer
      第22回日本時間生物学会学術大会
    • Place of Presentation
      東京大学(文京区、東京都)
    • Year and Date
      2015-11-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] 細胞時計の新しい同調刺激の探索とそのシグナリング解析2015

    • Author(s)
      今村聖路、吉種光、深田吉孝
    • Organizer
      第22回日本時間生物学会学術大会
    • Place of Presentation
      東京大学(文京区、東京都)
    • Year and Date
      2015-11-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] 時計シスエレメント D-box を介したゲノムワイドな転写制御機構の解析2015

    • Author(s)
      浅野吉政、吉種光、尾崎遼、鈴木穣、寺嶋秀騎、佐上彩、岩崎渉、深田吉孝
    • Organizer
      第22回日本時間生物学会学術大会
    • Place of Presentation
      東京大学(文京区、東京都)
    • Year and Date
      2015-11-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] インタラクトーム解析によるマウス CLOCK-BMAL1 の調節因子の探索2015

    • Author(s)
      広瀬健太郎、吉種光、杉山康憲、秦裕子、尾山大明、深田吉孝
    • Organizer
      第22回日本時間生物学会学術大会
    • Place of Presentation
      東京大学(文京区、東京都)
    • Year and Date
      2015-11-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] FBXL21 によるユビキチン化を介した CRY タンパク質の安定化メカニズムの解明2015

    • Author(s)
      野辺加織、吉種光、平野有沙、中川智貴、弓本佳苗、中山敬一、深田吉孝
    • Organizer
      第22回日本時間生物学会学術大会
    • Place of Presentation
      東京大学(文京区、東京都)
    • Year and Date
      2015-11-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] CRY タンパク質の多面的な安定性制御は概日時計の発振速度を調節する2015

    • Author(s)
      中川智貴、平野有沙、吉種光、尾山大明、秦裕子、ランジャコーンシリパン ダーリン 、深田吉孝
    • Organizer
      第22回日本時間生物学会学術大会
    • Place of Presentation
      東京大学(文京区、東京都)
    • Year and Date
      2015-11-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] Circadian epitranscriptomics: Mrna rhythms driven by rhythmic post-transcriptional regulation.2015

    • Author(s)
      Hikari Yoshitane, Hideki Terajima, Yoshitaka Fukada
    • Organizer
      EBRS-WCC Congress 2015
    • Place of Presentation
      Manchester, UK
    • Year and Date
      2015-08-03
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] リズミックなA-to-I RNA編集が担う体内時計機構の分子基盤2015

    • Author(s)
      寺嶋秀騎、吉種光、尾崎遥、鈴木穣、榛葉繁紀、岩崎渉、深田吉孝
    • Organizer
      第17回日本RNA学会年会
    • Place of Presentation
      ホテルライフォート札幌(札幌市、北海道)
    • Year and Date
      2015-07-15
    • Related Report
      2015 Annual Research Report
  • [Presentation] Circadian control of RNA modification regulates rhythmic gene expression and clock speed.2015

    • Author(s)
      Hideki Terajima, Hikari Yoshitane, Haruka Ozaki, Yutaka Suzuki, Shigeki Shimba, Wataru Iwasaki, and Yoshitaka Fukada
    • Organizer
      Gordon Research Conferences on Chronobiology
    • Place of Presentation
      Girona, Spain
    • Year and Date
      2015-06-01
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 新しいバイオインフォマティクス技術MOCCSを用いた転写因子CLOCKのDNA結合モチーフの決定.2014

    • Author(s)
      吉種 光
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川)
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Research-status Report
  • [Presentation] ゲノムワイドなCLOCKの標的探索が明らかにしたリズミックな転写後制御2014

    • Author(s)
      寺嶋 秀騎
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川)
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Research-status Report
  • [Presentation] 高浸透圧刺激による時計リセットシグナリングおよび遺伝子応答の解析2014

    • Author(s)
      今村 聖路
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川)
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Research-status Report
  • [Presentation] Resetting of the circadian clock with rapid induction of mammalian E4bp4 gene.2014

    • Author(s)
      Aya Sagami
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川)
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Research-status Report
  • [Presentation] マウス肝臓の概日時計を制御する転写因子複合体のプロテオミクス解析2014

    • Author(s)
      広瀬 健太郎
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川)
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Research-status Report
  • [Presentation] OMICS approach toward the mammalian circadian clockwork2014

    • Author(s)
      Hikari Yoshitane
    • Organizer
      第21回日本時間生物学会学術大会
    • Place of Presentation
      九州大学
    • Year and Date
      2014-11-07 – 2014-11-09
    • Related Report
      2014 Research-status Report
  • [Presentation] 時計因子CLOCKが生み出す転写リズムとリズミックな転写後制御の重要性2014

    • Author(s)
      寺嶋 秀騎
    • Organizer
      第21回日本時間生物学会学術大会
    • Place of Presentation
      九州大学
    • Year and Date
      2014-11-07 – 2014-11-09
    • Related Report
      2014 Research-status Report
  • [Presentation] DBP の DNA 結合領域の網羅的解析とその翻訳後修飾の制御2014

    • Author(s)
      布川 莉奈
    • Organizer
      第21回日本時間生物学会学術大会
    • Place of Presentation
      九州大学
    • Year and Date
      2014-11-07 – 2014-11-09
    • Related Report
      2014 Research-status Report
  • [Presentation] 新しいバイオインフォマティクス技術MOCCSを用いた転写因子CLOCKのDNA結合モチーフの決定2014

    • Author(s)
      吉種 光
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      国立京都国際会館(京都)
    • Year and Date
      2014-10-16 – 2014-10-18
    • Related Report
      2014 Research-status Report
  • [Presentation] Genome-wide approach for molecular outputs of the circadian clock in mice.2014

    • Author(s)
      Hikari Yoshitane
    • Organizer
      Chile-Japan Academic Forum in UTokyo Workshop on Genes, Cells and Organisms
    • Place of Presentation
      東京大学
    • Year and Date
      2014-10-08
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Molecular network of mammalian circadian clockwork2014

    • Author(s)
      吉種 光
    • Organizer
      WPI-IIIS 第44回セミナー
    • Place of Presentation
      筑波大学
    • Year and Date
      2014-10-07
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] A new method, MOCCS analysis, for determination of CLOCK-binding motifs.2014

    • Author(s)
      Hikari Yoshitane
    • Organizer
      The 30th Anniversary Meeting Sapporo Symposium on Biological Rhythm
    • Place of Presentation
      北海道大学
    • Year and Date
      2014-07-26 – 2014-07-27
    • Related Report
      2014 Research-status Report
  • [Presentation] MOCCS analysis for determination of CLOCK-binding motifs.2014

    • Author(s)
      Hikari Yoshitane
    • Organizer
      SRBR 2014(Society for Research on Biological Rhythms)
    • Place of Presentation
      Montana (USA)
    • Year and Date
      2014-06-13 – 2014-06-20
    • Related Report
      2014 Research-status Report
  • [Presentation] CLOCK ChIP-Seq and Circadian Transcriptome in the Mouse Liver.2013

    • Author(s)
      Hikari Yoshitane
    • Organizer
      Gordon Research Conferences:Chronobiology
    • Place of Presentation
      Rhode Island, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] Reexamine the functional roles of E4bp4 in the mammalian circadian clock.2013

    • Author(s)
      Aya Sagami
    • Organizer
      Gordon Research Conferences:Chronobiology
    • Place of Presentation
      Rhode Island, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] CLOCK-controlled multiple regulations of circadian rhythms through canonical and noncanonical E-boxes.2013

    • Author(s)
      Hideki Trajima
    • Organizer
      European Biological Rhythms Society
    • Place of Presentation
      Munchen, Germany
    • Related Report
      2013 Research-status Report
  • [Presentation] E4bp4-mediated phase-resetting signals to the circadian clock in mice.2013

    • Author(s)
      佐上 彩
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜市 パシフィコ横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] Analysis of the circadian phase-shift induced by hyperosmotic stress.2013

    • Author(s)
      今村 聖路
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜市 パシフィコ横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] CLOCK-ChIP-Seq and Circadian Transcriptome in the Mouse Liver.2013

    • Author(s)
      寺嶋 秀騎
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜市 パシフィコ横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] Clock protein complex that regulates the circadian transcriptional cycle in mouse liver.2013

    • Author(s)
      広瀬 健太郎
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜市 パシフィコ横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] Proteomics Approaches to Understand Molecular Basis of Mammalian Circadian Clock.2013

    • Author(s)
      広瀬健太郎
    • Organizer
      12th Human Proteome Organization Congress
    • Place of Presentation
      横浜市 パシフィコ横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] 多様な時計シスエレメントを介した概日リズムの多重制御.2013

    • Author(s)
      吉種 光
    • Organizer
      第20回日本時間生物学術大会
    • Place of Presentation
      東大阪市 近畿大学東大阪キャンパス
    • Related Report
      2013 Research-status Report
  • [Presentation] 時計タンパク質CLOCKとBMAL1のリン酸化リズムとその制御.2013

    • Author(s)
      吉種 光
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸市 神戸ポートアイランド
    • Related Report
      2013 Research-status Report
  • [Book] ブルーライトテキストブック2016

    • Author(s)
      吉種光、深田吉孝
    • Publisher
      金原出版
    • Related Report
      2015 Annual Research Report
  • [Book] Protein modifications pace the circadian oscillation of biological clocks2015

    • Author(s)
      Hikari Yoshitane and Yoshitaka Fukada
    • Publisher
      Springer
    • Related Report
      2015 Annual Research Report
  • [Book] ブレインサイエンス・レビュー 20152015

    • Author(s)
      吉種光
    • Publisher
      ブレインサイエンス振興財団
    • Related Report
      2015 Annual Research Report 2014 Research-status Report
  • [Book] Protein Modifications in Pathogenic Dysregulation of Signaling2015

    • Author(s)
      Hikari Yoshitane and Yoshitaka Fukada
    • Publisher
      Springer
    • Related Report
      2014 Research-status Report
  • [Remarks] 深田研ホームページ

    • URL

      http://www.biochem.s.u-tokyo.ac.jp/fukada-lab/

    • Related Report
      2015 Annual Research Report
  • [Remarks] Japan Prize 研究者ブログ

    • URL

      http://blog2015yoshitane.japanprize.jp

    • Related Report
      2015 Annual Research Report
  • [Remarks] 深田研ホームページ

    • URL

      http://www.biochem.s.u-tokyo.ac.jp/fukada-lab/index-j.html

    • Related Report
      2014 Research-status Report
  • [Remarks] 東京大学理学部 Research news

    • URL

      http://www.u-tokyo.ac.jp/ja/utokyo-research/research-news/molecular-mechanism-behind-circadian-rhythm/

    • Related Report
      2014 Research-status Report
  • [Remarks] 研究室ホームページ 研究ハイライト

    • URL

      http://www.biochem.s.u-tokyo.ac.jp/fukada-lab/research-highlights/rh2008/yoshitane2014-j.html

    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2022-01-31  

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