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2013 Fiscal Year Final Research Report

Analysis of mechanism involved in the assembly balance between centromere chromatin and/or heterochromatin and in higher cellular regulation.

Research Project

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Project/Area Number 23247030
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Molecular biology
Research InstitutionKazusa DNA Research Institute

Principal Investigator

MASUMOTO Hiroshi  公益財団法人かずさDNA研究所, ヒトゲノム研究部, 室長 (70229384)

Co-Investigator(Renkei-kenkyūsha) NAKANO Megumi  (公益財団法人)かずさDNA 研究所, 研究員 (50542825)
OHZEKI Jun-ichirou  (公益財団法人)かずさDNA 研究所, 研究員 (30514088)
Project Period (FY) 2011-04-01 – 2014-03-31
Keywords遺伝学 / 染色体 / ヘテロクロマチン / セントロメア / 人工染色体
Research Abstract

We investigated mechanism involved in the chromatin assembly balance between centromere chromatin and/or heterochromatin at human centromeric repetitive alphoid DNA. We found that tethering of histone acetyltransferases (HATs) to alphoid DNA arrays broke a cell type-specific barrier (heterochromatin formation) for de novo stable CENP-A chromatin assembly and induced assembly of stable Human Artificial Chromosomes (HACs) with the input alphoid DNA. We, then, tethered a huge variety of tetR-fusion proteins to the tetO-alphoid HAC and screened many positive and negative regulators for the CENP-A chromatin assembly using KAZUSA full-length cDNA library. We also developed a system targeting the chromatin assembly balance at endogenous centromeres by fusing these regulators and CENP-B.

  • Research Products

    (28 results)

All 2014 2013 2012 2011 Other

All Journal Article (16 results) (of which Peer Reviewed: 14 results) Presentation (9 results) (of which Invited: 5 results) Book (1 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] The epigenetic regulator Uhrf1 facilitates the proliferation and maturation of colonic regulatory T cells2014

    • Author(s)
      Obata Y, Furusawa Y, Endo TA, Sharif J, Takahashi D, Atarashi K, Nakayama M, Onawa S, Fujimura Y, Takahashi M, Ikawa T, Otsubo T, Kawamura YI, Dohi T, Tajima S, Masumoto H, Ohara O, Honda K, Hori S, Ohno H, Koseki H, Hase K
    • Journal Title

      Nat Immunol. Apr 28.

      Volume: 15 Pages: 571-579

    • Peer Reviewed
  • [Journal Article] Human artificial chromosome based gene delivery vectors for biomedicine and biotechnology2014

    • Author(s)
      Kouprina N, Tomilin AN, Masumoto H, Earnshaw WC, and Larionov V
    • Journal Title

      Expert Opin. Drug Deliv. 総説

      Volume: 11(4) Pages: 517-35

    • Peer Reviewed
  • [Journal Article] Identification of Novel α-N-Methylation Modification of CENP-B That Regulates Its Binding to the Centromeric DNA2013

    • Author(s)
      Dai X, Otake K, You C, Cai Q, Wang Z, Masumoto H and Wang Y
    • Journal Title

      J Proteome Res. Sep 6

      Volume: 12(9) Pages: 4167-75

    • Peer Reviewed
  • [Journal Article] A new assay for measuring chromosome instability (CIN) and identification of drugs that elevate CIN in cancer cells2013

    • Author(s)
      Lee H-S, Lee NC, Grimes BR, Samoshkin A, Kononenko AV, Bansal R, Masumoto H, Earnshaw WC, Kouprina N, Larionov V
    • Journal Title

      BioMed Central Cancer, May 22

      Volume: 13(1) Pages: 252

    • Peer Reviewed
  • [Journal Article] Protecting a transgene expression from the HAC-based vector by different chromatin insulators2013

    • Author(s)
      Lee NC, Kononenko AV, Lee H-S, Tolkunova EN, Liskovykh MA, Masumoto H, Earnshaw WC, Tomilin AN, Larionov V, Kouprina N
    • Journal Title

      Cell Mol Life Sci., Oct

      Volume: 70(19) Pages: 3723-37

    • Peer Reviewed
  • [Journal Article] Nap1 regulates proper CENP-B binding to nucleosomes2013

    • Author(s)
      Tachiwana H, Miya Y, Shono N, Ohzeki J, Osakabe A, Otake K, Larionov V, Earnshaw WC, Masumoto H and Kurumizaka H
    • Journal Title

      Nucleic. Acid. Res.

      Volume: 41(5) Pages: 2869-2880

    • Peer Reviewed
  • [Journal Article] Esperanto for histones : CENP-A, not CenH3, is the centromeric histone H3 variant2013

    • Author(s)
      Earnshaw WC, Allshire RC, Black BE, Bloom K, Brinkley BR, Brown W, Cheeseman IM, Choo KHA, Copenhaver GP, DeLuca JG, Desai A, Diekmann S, Erhardt S, Fitzgerald-Hayes M, Foltz D, Fukagawa T, Gassmann R, Gerlich DW, Glover DM, Gorbsky GJ, Harrison SC, Heun P, Hirota T, Jansen LET, Karpen G, Kops GJPL, Lampson MA, Lens SM, Losada A, Luger K, Maiato H, Maddox PS, Margolis RM, Masumoto H, McAinsh AD, Mellone BG, Meraldi P, Musacchio A, Oegema K, O'Neill RJ, Salmon ED, Scott KC, Straight AF, Stukenberg PT, Sullivan BA, Sullivan KF, Sunkel CE, Swedlow JR, Walczak CE, Warburton PE, Westermann S, Willard HF, Wordeman L, Yanagida M, Yen TJ, Yoda K, Cleveland DW
    • Journal Title

      Chromosome Res. 総説

      Volume: 21(2) Pages: 101-106

    • Peer Reviewed
  • [Journal Article] A new generation of human artificial chromosomes for functional genomics and gene therapy2013

    • Author(s)
      Kouprina N, Earnshaw WC, Masumoto H, and Larionov V
    • Journal Title

      Cell. Mol. Life Sci. 総説

      Volume: 70(7) Pages: 1135-48

  • [Journal Article] Centromere Architecture Breakdown Induced by the Viral E3 Ubiquitin Ligase ICP0 Protein of Herpes Simplex Virus Type 12012

    • Author(s)
      Gross S, Catez F, Masumoto H and Lomonte P
    • Journal Title

      PLOS ONE

      Volume: 7(9) Pages: e44227

    • Peer Reviewed
  • [Journal Article] Organization of Synthetic Alphoid DNA Array in Human Artifcial Chromosome (HAC) with a Conditional Centromere2012

    • Author(s)
      Kouprina N, Samoshkin A, Erliandri I, Nakano M, Lee H-S, Fu H, Iida Y, Aladjem M, Oshimura M, Masumoto H, Earnshaw WC and Larionov V
    • Journal Title

      ACS Synth.Biol.

      Volume: 1(12) Pages: 590-601

    • Peer Reviewed
  • [Journal Article] HACking the centromere chromatin code : insights from human artificial chromosomes2012

    • Author(s)
      Bergmann JH, Martins NM, Larionov V, Masumoto H, Earnshaw WC
    • Journal Title

      Chromosome Res.

      Volume: 20(5) Pages: 505-519

  • [Journal Article] Breaking the HAC Barrier : Histone H3K9 acetyl/methyl balance regulates CENP-A assembly2012

    • Author(s)
      Ohzeki J, Bergmann JH, Kouprina N, Noskov V, Nakano M, Kimura H, Earnshaw WC, Larionov V and Masumoto H
    • Journal Title

      EMBO J

      Volume: 31(10) Pages: 2391-2402

    • Peer Reviewed
  • [Journal Article] Epigenetic Engineering : Histone H3K9 acetylation is compatible with kinetochore structure and function2012

    • Author(s)
      Bergmann JH, Jakubsche J, Martins NM, Nakano M, Kimura H, Kelly DA, Turner BM, Masumoto H, Larionov V and Earnshaw WC
    • Journal Title

      J. Cell Science

      Volume: 125(Pt 2) Pages: 411-421

    • Peer Reviewed
  • [Journal Article] HP1γ links histone methylation marks to meiotic synapsis in mice2011

    • Author(s)
      Takada Y, Naruse C, Costa Y, Shirakawa T, Tachibana M, Sharif J, Kezuka-Shiotani F, Kakiuchi D, Masumoto H, Shinkai Y, Ohbo K, Peters AH, Turner JM, Asano M, Koseki
    • Journal Title

      Development.

      Volume: 138 Pages: 4207-17

    • Peer Reviewed
  • [Journal Article] Human Artificial Chromosome (HAC) vector with a conditional centromere for correction of genetic deficiencies in human cells2011

    • Author(s)
      Kim J-H, Kononenko A, Erliandri I, Kim T, Nakano M, Iida Y, Barrett CJ, Oshimura M, Masumoto H, Earnshaw WC, Larionov V & Kouprina N
    • Journal Title

      PNAS

      Volume: 108 Pages: 20048-53

    • Peer Reviewed
  • [Journal Article] Epigenetic engineering shows H3K4me2 is required for HJURP targeting and CENP-A assembly on a synthetic human kinetochore2011

    • Author(s)
      Bergmann JH, Rodriguez MG, Martins NMC, Kimura H, Kelly DA, Masumoto H, Larionov V, Jansen LET and Earnshaw WC
    • Journal Title

      EMBO J.

      Volume: 30 Pages: 328-340

    • Peer Reviewed
  • [Presentation] ヒト人工染色体を用いたセントロメアとヘテロクロマチンの集合機構の解析2014

    • Author(s)
      舛本寛
    • Organizer
      高等研プロジェクト第1回「クロマチン・デコーディング」研究会
    • Place of Presentation
      国際高等研
    • Year and Date
      20140328-30
    • Invited
  • [Presentation] Exploring of centromere acetylating mechanism using tetO-alphoid system2012

    • Author(s)
      Ohzeki J, Shono N, Otake K, Nakano M, Earnshaw WC, Larionov V, Nagase T, Masumoto H
    • Organizer
      第30回染色体ワークショップ、第11回核ダイナミクス研究会
    • Place of Presentation
      淡路夢舞台国際会議(口頭発表)
    • Year and Date
      20121219-21
  • [Presentation] Analysis of centromere chromatin assembly using tetO/tetR synthetic DNA system2012

    • Author(s)
      Shono N, Ohzeki J, Nakano M, Nagase T, Earnshaw WC, Larionov V, Masumoto H
    • Organizer
      第35回日本分子生物学会
    • Place of Presentation
      福岡国際会議場(口頭発表)
    • Year and Date
      20121211-14
  • [Presentation] 細胞へ導入されたDNAの運命 : 人工染色体形成、宿主染色体への組込み、核からの脱落、はどのように起こるか?2012

    • Author(s)
      舛本寛、大関淳一郎、中野めぐみ、Larionov V and Earnshaw WC
    • Organizer
      第84回日本遺伝学会大会
    • Place of Presentation
      博多
    • Year and Date
      20120924-26
    • Invited
  • [Presentation] Heterochromatin assembly balance determines the fate of de novo kinetochre formation on satellite DNA(ミニシンポジウム主催)2012

    • Author(s)
      Masumoto H, Ohzeki J, Nakano M, Vladimir N, Kouprina N, Earnshaw WC and Larionov V
    • Organizer
      第63回日本細胞生物学会大会
    • Place of Presentation
      札幌
    • Year and Date
      20120627-29
  • [Presentation] Chromatin assembly balance determines the fate of de novo kinetochre formation on satellite DNA2011

    • Author(s)
      Masumoto H, Ohzeki J, Nakano M, Kouprina N, Larionov V, Earnshaw WC
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      20111213-16
    • Invited
  • [Presentation] A chromatin assembly balance on satellite DNA determines the fate of de novo kinetochore and HAC formation2011

    • Author(s)
      Masumoto H, Ohzeki J, Nakano M, Kouprina N, Larionov V and Earnshaw WC
    • Organizer
      Japanese-German JSPS and DFG-funded workshop "Centromeres and Artificial Chromosomes"
    • Place of Presentation
      Leibniz Institute of Plant Genetics and Crop Plant Research (IPK), Gatersleben, Germany
    • Year and Date
      20111031-1103
    • Invited
  • [Presentation] ヒト人工染色体を創って調べる2011

    • Author(s)
      舛本寛
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      京都
    • Year and Date
      20110921-23
    • Invited
  • [Presentation] セントロメアをアセチル化する機構の探索2011

    • Author(s)
      大関淳一郎、庄野暢晃、中野めぐみ、 William C. Earnshaw, Vladimir Larionov、長瀬隆弘、舛本寛
    • Organizer
      第29回染色体ワークショップ
    • Place of Presentation
      仙台(口頭)
    • Year and Date
      20110125-27
  • [Book] セントロメア形成を決定するクロマチン集合バランス, 生体の科62(5)2011

    • Author(s)
      舛本寛
    • Total Pages
      458-459
  • [Remarks]

    • URL

      http://www.kazusa.or.jp/j/laboratories/labo_cellengineering.html

  • [Patent(Industrial Property Rights)] A method for positively or negatively regulating the assembly of newly synthesized CENP-A to exogenous alphoid DNA containing CENP-B boxes in mammalian cell lines2012

    • Inventor(s)
      Masumoto H, Ohzeki J, Larionov V, Earnshaw WC
    • Industrial Property Rights Holder
      かずさDNA研究所
    • Industrial Property Rights Type
      PCT/JP2012/007384
    • Industrial Property Number
      No.61/562,825
    • Filing Date
      2012-11-22
    • Overseas

URL: 

Published: 2015-06-25  

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