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Understanding biological ignificance of histone modifications by epigenetic manipulation using multifunctional antibodies

Research Project

Project/Area Number 26291071
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Genetics/Chromosome dynamics
Research InstitutionTokyo Institute of Technology

Principal Investigator

Kimura Hiroshi  東京工業大学, 科学技術創成研究院, 教授 (30241392)

Project Period (FY) 2014-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥15,860,000 (Direct Cost: ¥12,200,000、Indirect Cost: ¥3,660,000)
Fiscal Year 2016: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2015: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2014: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywordsクロマチン / エピジェネティクス / 遺伝子発現制御 / 転写 / ヒストン修飾 / 細胞分裂 / 抗体 / 遺伝子 / 細胞・組織 / バイオテクノロジー / シグナル伝達 / ゲノム / エピジェネティクス制御 / 染色体
Outline of Final Research Achievements

DNA in eukaryotic nuclei forms chromatin by binding with histone proteins. Histones are subjected to a variety of posttranslational modifications, but the biological significance of those modifications remains largely unknown. In this study, we performed inhibitory assay based on antibody injection, identification of proteins that bind to specifically modified chromatin, and development of new live cell modification probes. When phosphorylated histone-specific probes were injected into cells, chromosome missegregation was observed, which probably resulted from bridging between sister chromatids. A candidate protein that bound to phsophorylated chromatin localized to centromeres. Finally, we developed some new modification-specific intracellular antibody probes that could monitor specific modifications in living cells.

Report

(5 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • 2014 Annual Research Report

Research Products

(44 results)

All 2018 2017 2016 2015 Other

All Int'l Joint Research (7 results) Journal Article (15 results) (of which Int'l Joint Research: 10 results,  Peer Reviewed: 13 results,  Open Access: 11 results,  Acknowledgement Compliant: 4 results) Presentation (12 results) (of which Int'l Joint Research: 5 results,  Invited: 12 results) Remarks (9 results) Patent(Industrial Property Rights) (1 results)

  • [Int'l Joint Research] キュリー研究所/ツールーズ大学(フランス)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] フロリダ州立大学/ロックフェラー大学(米国)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] エジンバラ大学(英国)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] Curie Institute/University of Toulouse(フランス)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] University of Edinburgh(英国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] University of Edinbrough(英国)

    • Related Report
      2015 Annual Research Report
  • [Int'l Joint Research] Max Delbruck Center(ドイツ)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] NOTCH-mediated non-cell autonomous regulation of chromatin structure during senescence2018

    • Author(s)
      Parry AJ, Hoare M, Bihary D, Hansel-Hertsch R, Smith S, Tomimatsu K, Mannion E, Smith A, D'Santos P, Russel IA, Balasubramanian S, Kimura H, Samarajiwa SA, Narita M.
    • Journal Title

      Nat Commun

      Volume: 9 Issue: 1 Pages: 1840-1840

    • DOI

      10.1038/s41467-018-04283-9

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] HP1α targets the chromosomal passenger complex for activation at heterochromatin before mitotic entry.2018

    • Author(s)
      Ruppert JG, Samejima K, Platani M, Molina O, Kimura H, Jeyaprakash AA, Ohta S, Earnshaw WC.
    • Journal Title

      EMBO J

      Volume: 37 Issue: 6

    • DOI

      10.15252/embj.201797677

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] HELLS and CDCA7 comprise a bipartite nucleosome remodeling complex defective in ICF syndrome.2018

    • Author(s)
      Jenness C, Giunta S, Muller MM, Kimura H, Muir TW, Funabiki H.
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: 115 Issue: 5

    • DOI

      10.1073/pnas.1717509115

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] H3S10ph broadly marks early-replicating domains in interphase ESCs and shows reciprocal antagonism with H3K9me2.2018

    • Author(s)
      Chen CCL, Goyal P, Karimi MM, Abildgaard MH, Kimura H, Lorincz MC.
    • Journal Title

      Genome Res

      Volume: 28 Issue: 1 Pages: 37-51

    • DOI

      10.1101/gr.224717.117

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Nucleosome stability measured in situ by automated quantitative imaging2017

    • Author(s)
      Imre L, Simandi Z, Horvath A, Fenyofalvi G, Nanasi P, Niaki EF, Hegedus E, Bacso Z, Weyemi U, Mauser R, Ausio J, Jeltsch A, Bonner W, Nagy L, Kimura H, Szabo G.
    • Journal Title

      Sci Rep

      Volume: 7 Issue: 1 Pages: 12743-12743

    • DOI

      10.1038/s41598-017-12608-9

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Semi-quantitative Analysis of H4K20mel Levels in Living Cells Using Mintbody2017

    • Author(s)
      Sato Y, Kimura H
    • Journal Title

      Bio-protocol

      Volume: 7 Issue: 10

    • DOI

      10.21769/bioprotoc.2276

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 3. Global histone modification fingerprinting in human cells using epigenetic reverse phase protein array2017

    • Author(s)
      Partolina M, Thoms HC, MacLeod KG, Rodriguez-Blanco G, Clarke MN, Venkatasubramani AV, Beesoo R, Larionov V, Neergheen-Bhujun VS, Serrels B, Kimura H, Carragher NO, Kagansky A.
    • Journal Title

      Cell Death Discov

      Volume: 3 Issue: 1 Pages: 16077-16077

    • DOI

      10.1038/cddiscovery.2016.77

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Nucleome研究の世界動向2017

    • Author(s)
      田代 聡、木村 宏
    • Journal Title

      実験医学

      Volume: 35 Pages: 78-82

    • Related Report
      2016 Annual Research Report
  • [Journal Article] A genetically encoded probe for live-cell imaging of H4K20 monomethylation2016

    • Author(s)
      Sato Y., Kujirai T., Arai R., Asakawa H., Ohtsuki C., Horikoshi N., Yamagata K., Ueda J., Nagase T., Haraguchi T., Hiraoka Y., Kimura A., Kurumizaka H., Kimura, H.
    • Journal Title

      J. Mol. Biol.

      Volume: 428 Issue: 20 Pages: 3885-3902

    • DOI

      10.1016/j.jmb.2016.08.010

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Histone H4 lysine 20 acetylation is associated with gene repression in human cells.2016

    • Author(s)
      Kaimori, J. Y., Maehara, K., Hayashi-Takanaka, Y., Harada, A., Fukuda, M., Yamamoto, S., Ichimaru, N., Umehara, T., Yokoyama, S., Matsuda, R., Ikura, T., Nagao, K., Obuse, C., Nozaki, N., Takahara, S., Takao, T., Ohkawa, Y., Kimura, H., and Isaka, Y.
    • Journal Title

      Sci Rep.

      Volume: 6 Issue: 1 Pages: 24318-24318

    • DOI

      10.1038/srep24318

    • NAID

      120005770760

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] エピゲノム解析手法の標準化:ヒストン修飾解析2016

    • Author(s)
      木村 宏
    • Journal Title

      実験医学増刊『エピゲノム研究:修飾の全体像の理解から先制・個別化医療へ』

      Volume: 34 Pages: 32-37

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Epigenetic engineering shows that a human centromere resists silencing mediated by H3K27me3/K9me3.2016

    • Author(s)
      Martins NMC, Bergmann JH, Shono N, Kimura H, Larionov V, Masumoto H and Earnshaw WC.
    • Journal Title

      Mol Biol Cell

      Volume: 27 Issue: 1 Pages: 177-196

    • DOI

      10.1091/mbc.e15-08-0605

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Methylation of RNA polymerase II non-consensus Lysine residues marks early transcription in mammalian cells.2015

    • Author(s)
      Dias JD, Rito T, Torlai Triglia E, Kukalev A, Ferrai C, Chotalia M, Brookes E, Kimura H, Pombo A
    • Journal Title

      eLIFE

      Volume: 4

    • DOI

      10.7554/elife.11215

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] CENP-C and CENP-I are key connecting factors for kinetochore and CENP-A assembly.2015

    • Author(s)
      Shono N, Ohzeki J, Otake K, Martins NMC, Nagase T, Kimura H, Larionov V, Earnshaw WC, Masumoto H.
    • Journal Title

      J Cell Sci.

      Volume: 128 Pages: 4572-4587

    • DOI

      10.1242/jcs.180786

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Distribution of histone H4 modifications as revealed by a panel of specific monoclonal antibodies.2015

    • Author(s)
      Hayashi-Takanaka Y., Maehara K., Harada A., Umehara T., Yokoyama S., Obuse C., Ohkawa Y., Nozaki N., Kimura H.
    • Journal Title

      Chromosome Res.

      Volume: 23 Issue: 4 Pages: 753-766

    • DOI

      10.1007/s10577-015-9486-4

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Chromatin modification dynamics during gene activation in living cells2017

    • Author(s)
      木村宏
    • Organizer
      4D Nucleome : The Cell Nucleus in Space and Time
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Chromatin modification dynamics during gene activation in living cells2017

    • Author(s)
      木村宏
    • Organizer
      10th Berlin Summer Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Chromatin modification dynamics during cell differentiation2017

    • Author(s)
      木村宏
    • Organizer
      Gordon Research Conference “Genome Architecture in Cell Fate & Disease”
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Chromatin modification dynamics during cell differentiation2017

    • Author(s)
      木村宏
    • Organizer
      HMGU-Japan Epigenetics and Chromatin Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Chromatin Integration Labeling Technology2017

    • Author(s)
      木村宏
    • Organizer
      平成29年度遺伝研研究会『エピジェネティクスの基盤となるクロマチン・細胞核の動的構造変換』
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] クロマチン修飾ダイナミクスと転写制御2017

    • Author(s)
      木村宏
    • Organizer
      第40回日本分子生物学会年会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] クロマチン修飾動態解析によるクレオーム研究2017

    • Author(s)
      木村 宏
    • Organizer
      よこはまMNR研究会主催 第56回ワークショップ
    • Place of Presentation
      横浜市
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Live cell imaging of histone and RNA polymerase II modifications2016

    • Author(s)
      Hiroshi Kimura
    • Organizer
      第39回 日本分子生物学会年会シンポジウム『ヌクレオーム研究の幕開け』
    • Place of Presentation
      横浜市
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 転写活性化におけるヒストン修飾の役割2016

    • Author(s)
      木村 宏
    • Organizer
      遺伝研研究会『クロマチン・細胞核の動的構造変換とエピジェネティクス制御
    • Place of Presentation
      三島市
    • Year and Date
      2016-10-27
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Visualizing protein modifications in vivo2016

    • Author(s)
      木村 宏
    • Organizer
      新学術領域研究『環境記憶統合』第2回若手の会
    • Place of Presentation
      熱海市
    • Year and Date
      2016-10-13
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Tracking posttranslational and epigenetic modifications of endogenous proteins in vivo2015

    • Author(s)
      Hiroshi Kimura
    • Organizer
      24th Wilhelm Bernhard Workshop on the Cell Nucleus/57th Symposium of the Society for Histochemistry
    • Place of Presentation
      Schloss Wilhelminenberg, Vienna, Austria
    • Year and Date
      2015-08-20
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] エピゲノム修飾の生細胞・生体内ダイナミクス2015

    • Author(s)
      木村 宏
    • Organizer
      第9回日本エピジェネティクス研究会
    • Place of Presentation
      学術総合センター
    • Year and Date
      2015-05-25
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Remarks] 木村宏 研究室

    • URL

      http://kimura-lab.bio.titech.ac.jp/index.html

    • Related Report
      2017 Annual Research Report
  • [Remarks] 東工大 木村宏 研究者情報

    • URL

      http://t2r2.star.titech.ac.jp/cgi-bin/researcherinfo.cgi?q_researcher_content_number=CTT100673940#

    • Related Report
      2017 Annual Research Report
  • [Remarks] 東工大 細胞制御工学研究センター

    • URL

      http://www.rcb.iir.titech.ac.jp/

    • Related Report
      2017 Annual Research Report
  • [Remarks] 東京工業大学 木村研究室

    • URL

      http://kimura-lab.bio.titech.ac.jp/

    • Related Report
      2016 Annual Research Report 2014 Annual Research Report
  • [Remarks] 東京工業大学 科学技術創成研究院 細胞制御工学研究センター

    • URL

      http://cell-biology.jimdo.com/

    • Related Report
      2016 Annual Research Report
  • [Remarks] 東京工業大学 リサーチリポジトリ 木村宏

    • URL

      http://t2r2.star.titech.ac.jp/cgi-bin/researcherinfo.cgi?q_researcher_content_number=CTT100673940

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
  • [Remarks] 東京工業大学 木村宏研究室

    • URL

      http://kimura-lab.bio.titech.ac.jp/

    • Related Report
      2015 Annual Research Report
  • [Remarks] 東京工業大学 科学技術創成研究院 細胞制御工学ユニット

    • URL

      http://cell-biology.jimdo.com/

    • Related Report
      2015 Annual Research Report
  • [Remarks] 東京工業大学 生命理工学研究科 木村研究室

    • URL

      http://www.bio.titech.ac.jp/laboratory/kimura-kajikawa/kimura/index.html

    • Related Report
      2014 Annual Research Report
  • [Patent(Industrial Property Rights)] ヒストンH3トリメチル化リシン特異的モノクローナル抗体又はその抗原結合性断片2017

    • Inventor(s)
      木村 宏、佐藤優子、大井彰人、胡桃坂仁志、鯨井智也、他
    • Industrial Property Rights Holder
      東京工業大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2017-111580
    • Filing Date
      2017
    • Related Report
      2017 Annual Research Report

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Published: 2014-04-04   Modified: 2022-02-28  

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