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Study on nucleosomes and chromatin-demodifying enzymes

Research Project

Project/Area Number 24613007
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field epigenetics
Research InstitutionThe Institute of Physical and Chemical Research

Principal Investigator

UMEHARA Takashi  独立行政法人理化学研究所, ライフサイエンス技術基盤研究センター, ユニットリーダー (20415095)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords遺伝子発現 / エピジェネティクス / エピゲノム / クロマチン / 染色体 / ヒストン / ヌクレオソーム / 構造解析 / 転写 / メチル化 / 阻害剤
Outline of Final Research Achievements

Purpose of this study is to establish biochemical assay systems for understanding of regulatory mechanisms of lysine-methylated nucleosome core particles through the histone demethylase family of LSD1/LSD2 (Lysine-specific demethylase-1/2) which is assumed in the onsets of intractable cancers and/or lifestyle-related diseases. We achieved cell-free protein production methodology to synthesize full-length histone H3 protein containing a site-specific mono-methyl-lysine, which is the demethylation substrates for LSD1/LSD2 in the context of chromatin, through the combination of site-specific incorporation of Boc-protected mono-methyl-lysine into a protein during translation and chemical removal of the Boc group.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (34 results)

All 2015 2014 2013 2012 Other

All Journal Article (9 results) (of which Peer Reviewed: 7 results,  Acknowledgement Compliant: 2 results,  Open Access: 4 results) Presentation (19 results) (of which Invited: 4 results) Book (2 results) Remarks (4 results)

  • [Journal Article] New Frontiers of Epigenetics Researches in Pharmaceutical Sciences2015

    • Author(s)
      Umehara. T., Hori, Y.
    • Journal Title

      YAKUGAKU ZASSHI

      Volume: 135 Issue: 1 Pages: 1-2

    • DOI

      10.1248/yakushi.14-00202-F

    • NAID

      130004756463

    • ISSN
      0031-6903, 1347-5231
    • Year and Date
      2015-01-01
    • Related Report
      2014 Annual Research Report
    • Open Access
  • [Journal Article] Lysine-specific demethylase LSD2 suppresses lipid influx and metabolism in hepatic cells2015

    • Author(s)
      Nagaoka, K., Hino, S., Sakamoto, A., Anan, K., Takase, R., Umehara, T., Yokoyama, S., Sasaki, Y., Nakao, M.
    • Journal Title

      Mol. Cell. Biol.

      Volume: 35 (7) Issue: 7 Pages: 1068-1080

    • DOI

      10.1128/mcb.01404-14

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Solution structures of the DNA-binding domains of immune-related zinc-finger protein ZFAT2015

    • Author(s)
      *Tochio, N., *Umehara, T., Nakabayashi, K., Yoneyama, M., Tsuda, K., Shirouzu, M., Koshiba, S., Watanabe, S., Kigawa, T., Sasazuki, T., Shirasawa, S., Yokoyama, S.
    • Journal Title

      J. Struct. Funct. Genomics

      Volume: 16 (2)

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Multiple site-specific installations of N(ε)-monomethyl-L-lysine into histone proteins by cell-based and cell-free protein synthesis2014

    • Author(s)
      Yanagisawa, T., Takahashi, M., Mukai, T., Sato, S., Wakamori, M., Shirouzu, M., Sakamoto, K., and Umehara, T. and Yokoyama, S.
    • Journal Title

      ChemBioChem

      Volume: 15 Issue: 12 Pages: 1830-1838

    • DOI

      10.1002/cbic.201402291

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Expanded genetic code technologies for modified lysine installation at multiple sites2014

    • Author(s)
      Yanagisawa, T., Umehara, T., Sakamoto, K., and Yokoyama, S.
    • Journal Title

      ChemBioChem

      Volume: 15 Issue: 15 Pages: 2181-2187

    • DOI

      10.1002/cbic.201402266

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of a hexahistidine-3× FLAG-tandem affinity purification method for endogenous protein complexes in Pichia pastoris2014

    • Author(s)
      Toshiaki Higo, Noriyuki Suka, Haruhiko Ehara, Masatoshi Wakamori, Shin Sato, Hideaki Maeda, Shun-ichi Sekine, Takashi Umehara, and Shigeyuki Yokoyama
    • Journal Title

      J Struct Funct Genomics

      Volume: 15 Issue: 4 Pages: 191-199

    • DOI

      10.1007/s10969-014-9190-1

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Structures of histone methyltransferase SET7/9 in complexes with adenosylmethionine derivatives2013

    • Author(s)
      Hideaki Niwa, Noriko Handa, Yuri Tomabechi, Keiko Honda, Mitsutoshi Toyama, Noboru Ohsawa, Mikako Shirouzu, Hiroyuki Kagechika, Tomoya Hirano, Takashi Umehara, Shigeyuki Yokoyama
    • Journal Title

      Acta Crystallographica Section D

      Volume: 69 Issue: 4 Pages: 595-602

    • DOI

      10.1107/s0907444912052092

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] A tandem insertion vector for large-scale preparation of nucleosomal DNA2012

    • Author(s)
      Wakamori, M., Umehara, T., Yokoyama, S.
    • Journal Title

      Anal.Biochem.

      Volume: (印刷中) Issue: 1 Pages: 184-186

    • DOI

      10.1016/j.ab.2012.01.010

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Structural biology toward rational drug development in collaboration with molecular imaging2012

    • Author(s)
      Umehara, T., Shirouzu, M., Yokoyama, S.
    • Journal Title

      Curr. Med. Imaging Rev.

      Volume: 8 Issue: 4 Pages: 308-313

    • DOI

      10.2174/157340512803759794

    • Related Report
      2012 Research-status Report
  • [Presentation] 「エピヌクレオソーム」の再構成に基づいた創薬技術開発」2015

    • Author(s)
      梅原崇史
    • Organizer
      第135回日本薬学会年会
    • Place of Presentation
      神戸市
    • Year and Date
      2015-03-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] Structure-based development of inhibitors targeting histone demethylase LSD1/KDM12014

    • Author(s)
      Umehara, T., Yokoyama, S.
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      横浜市
    • Year and Date
      2014-11-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] Functional and structural analyses of H4-acetylated nucleosome core particles2014

    • Author(s)
      Umehara, T., Wakamori, M., Fujii, Y., Suka, N., Shirouzu, M., Sakamoto, K., Yokoyama, S.
    • Organizer
      11th EMBL Conference of Transcription and Chromatin
    • Place of Presentation
      Heidelberg, Germany
    • Year and Date
      2014-08-24
    • Related Report
      2014 Annual Research Report
  • [Presentation] Synthesis of histone proteins containing multiple and site-specific monomethyl-lysines2014

    • Author(s)
      Umehara, T., Yanagisawa, T., Takahashi, M., Mukai, T., Sato, S., Wakamori, M., Shirouzu, M., Sakamoto, K., Yokoyama, S.
    • Organizer
      FASEB Science Research Conference on Biological Methylation: Regulation of Chromatin, Epigenetics, and Disease
    • Place of Presentation
      Nassau, Bahamas
    • Year and Date
      2014-07-07
    • Related Report
      2014 Annual Research Report
  • [Presentation] Reconstitution of ‘epi-nucleosomes’ with pinpoint epigenetic information2014

    • Author(s)
      Umehara, T., Yokoyama, S.
    • Organizer
      広島大学 クロマチン動態数理研究拠点セミナー
    • Place of Presentation
      広島市
    • Year and Date
      2014-06-13
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Structure-based development of epigenetics-regulating inhibitors and ‘Epi-nucleosomes’

    • Author(s)
      Takashi Umehara, Shin Sato, Hideaki Niwa, Masatoshi Wakamori, Kensaku Sakamoto, Mikako Shirouzu, Shigeyuki Yokoyama
    • Organizer
      7th International Conference on Structural Genomics
    • Place of Presentation
      Sapporo, Japan
    • Related Report
      2013 Research-status Report
  • [Presentation] Reconstitution of epigenetic nucleosomes through genetic code expansion

    • Author(s)
      Takashi Umehara, Masatoshi Wakamori, Mihoko Takahashi, Takahito Mukai, Mikako Shirouzu, Kensaku Sakamoto, Shigeyuki Yokoyama
    • Organizer
      The 65th Fujihara Seminar, International Symposium on Synthetic Biology of Unnatural Base Pairs and Amino Acids
    • Place of Presentation
      Tomakomai, Japan
    • Related Report
      2013 Research-status Report
  • [Presentation] 残基特異的な修飾を導入した「エピヌクレオソーム」の調製技術開発と機能解析

    • Author(s)
      梅原崇史, 若森昌聡, 須賀則之, 高橋美穂子, 佐藤 心, 柳沢達男, 向井崇人, 白水美香子, 坂本健作, 横山茂之
    • Organizer
      第7回日本エピジェネティクス研究会年会
    • Place of Presentation
      奈良市
    • Related Report
      2013 Research-status Report
  • [Presentation] 合理的創薬を指向したヒストン脱メチル化酵素LSD1/KDM1の構造基盤阻害剤開発

    • Author(s)
      梅原崇史, 日野信次朗, 佐藤 心, 丹羽英明, 白水美香子, 中尾光善, 横山茂之
    • Organizer
      日本ケミカルバイオロジー学会 第8回年会
    • Place of Presentation
      東京都文京区
    • Related Report
      2013 Research-status Report
  • [Presentation] BETファミリーのヒストン認識ポケットに対する構造基盤阻害剤開発

    • Author(s)
      梅原崇史, 横山茂之
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜市
    • Related Report
      2013 Research-status Report
  • [Presentation] 薬学が拓くエピジェネティクス研究の最前線

    • Author(s)
      梅原崇史, 堀雄一郎
    • Organizer
      第134回日本薬学会年会
    • Place of Presentation
      熊本市
    • Related Report
      2013 Research-status Report
  • [Presentation] Structural study and drug development of a histone demethylase involved in repressive KLF pathway

    • Author(s)
      Takashi Umehara
    • Organizer
      FASEB Summer Research Conference on Biology and Pathobiology of Krueppel-like Factors
    • Place of Presentation
      Base Village, Snowmass Village, CO, USA
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Structure analysis and drug development of transcription factor complexes

    • Author(s)
      Takashi Umehara and Shigeyuki Yokoyama
    • Organizer
      International Symposium on Development of Medical Technologies for Treating Intractable Cancers and Cardiovascular Diseases
    • Place of Presentation
      Univ. Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] 複数の残基特異的アセチル化を含む「エピヌクレオソーム」の再構成と機能解析

    • Author(s)
      梅原崇史, 若森昌聡, 須賀則之, 向井崇人, 寺田貴帆, 白水美香子, 坂本健作, 横山茂之
    • Organizer
      第6回日本エピジェネティクス研究会年会
    • Place of Presentation
      学術総合センター(東京都千代田区)
    • Related Report
      2012 Research-status Report
  • [Presentation] ヒストン脱メチル化酵素LSD1/KDM1の結晶構造解析と阻害剤開発

    • Author(s)
      梅原崇史, 三桝信哉, 佐藤 心, 須賀則之, 丹羽英明, 半田徳子, 横山茂之
    • Organizer
      第12回日本蛋白質科学会年会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Related Report
      2012 Research-status Report
  • [Presentation] エピジェネティックなヌクレオソームの調製技術

    • Author(s)
      梅原崇史
    • Organizer
      大阪大学蛋白質研究所セミナー
    • Place of Presentation
      大阪大学吹田キャンパス(大阪府吹田市)
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] クロマチンを創る:エピジェネティック情報を持つヌクレオソームの試験管内再構成

    • Author(s)
      梅原崇史, 若森昌聡, 須賀則之, 向井崇人, 寺田貴帆, 白水美香子, 坂本健作, 横山茂之
    • Organizer
      細胞を創る研究会5.0
    • Place of Presentation
      東京工業大学すずかけ台キャンパス(神奈川県横浜市)
    • Related Report
      2012 Research-status Report
  • [Presentation] 創薬を指向した疾患関連タンパク質とその阻害剤複合体のX線結晶構造解析

    • Author(s)
      梅原崇史, 丹羽英明, 半田徳子, 影近弘之, 平野智也, 白水美香子, 横山茂之
    • Organizer
      第30回Photon Factoryシンポジウム
    • Place of Presentation
      つくば国際会議場(茨城県つくば市)
    • Related Report
      2012 Research-status Report
  • [Presentation] 創薬を指向したエピジェネティクス研究の最前線

    • Author(s)
      梅原崇史
    • Organizer
      第133回日本薬学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Related Report
      2012 Research-status Report
  • [Book] 生体の科学 「生命動態システム科学」 エピヌクレオソームの再構成による遺伝子発現制御解析 65 (5) 462-4632014

    • Author(s)
      梅原崇史
    • Total Pages
      2
    • Publisher
      医学書院
    • Related Report
      2014 Annual Research Report
  • [Book] 「エピジェネティクスを標的とした医薬品開発」 構造活性相関部会ニュースレター No. 25, pp. 9-162013

    • Author(s)
      梅原崇史
    • Total Pages
      8
    • Publisher
      日本薬学会
    • Related Report
      2013 Research-status Report
  • [Remarks]

    • URL

      http://www.riken.jp/research/labs/clst/struct_synth_biol/bio_funct_mol_dev/epigen_drug_discov/

    • Related Report
      2014 Annual Research Report
  • [Remarks]

    • URL

      http://researchmap.jp/ume/

    • Related Report
      2014 Annual Research Report
  • [Remarks] 理化学研究所 ライフサイエンス技術基盤研究センター エピジェネティクス制御研究ユニット

    • URL

      http://www.clst.riken.jp/activity/structuralbiology_group2_team4.html

    • Related Report
      2013 Research-status Report
  • [Remarks] 理化学研究所 ライフサイエンス技術基盤研究センター エピジェネティクス制御研究ユニット

    • URL

      http://www.riken.jp/research/labs/clst/struct_synth_biol/bio_funct_mol_dev/epigen_drug_discov/

    • Related Report
      2012 Research-status Report

URL: 

Published: 2013-05-31   Modified: 2019-07-29  

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