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Functional analyses of chromatin structure changing-related factors in higher eukaryotic cells by gene targeting techniques

Research Project

Project/Area Number 19310127
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 基礎ゲノム科学
Research InstitutionUniversity of Miyazaki

Principal Investigator

NAKAYAMA Tatsuo  University of Miyazaki, 理事 (60031712)

Co-Investigator(Kenkyū-buntansha) TAKAMI Yasunari  宮崎大学, 医学部, 准教授 (80236356)
KIKUCHI Hidehiko  宮崎大学, 医学部, 助教 (10301384)
Project Period (FY) 2007 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥20,410,000 (Direct Cost: ¥15,700,000、Indirect Cost: ¥4,710,000)
Fiscal Year 2009: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2008: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
Fiscal Year 2007: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Keywordsヒストン / クロマチン / ヌクレオソーム / ジーンノックアウト法 / アポトーシス / 転写制御 / クロマチン構造 / ヒストンシャペロン / DNA複製 / 細胞周期 / チェックポイント / DNA障害 / DT40 / ジーンノックアスト法
Research Abstract

To clarify individual roles of chromatin structure changing-related factors in higher eukaryotic cells, we generated systematically a number of chicken DT40 mutant cell lines, respectively, lacking each of appropriate genes. By analyses of these mutant cells, we obtained important results as follows. (1) CAF-1-dependent nucleosome assembly is essential in DNA replication and cell proliferation via its interaction with PCNA. (2) HDAC2 regulates indirectly gene expressions of IgM H- and ・L chains via opposite controls of gene expressions of EBF1, Pax5, Aiolos plus Ikaros, and E2A. (3) GCN5 and BCR signaling regulate cooperatively pre-mature B cell apoptosis through both increases of caspase-3 and caspase-8 activities and decreases of ICAD and IAP2.

Report

(4 results)
  • 2009 Annual Research Report   Final Research Report ( PDF )
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • Research Products

    (52 results)

All 2011 2010 2009 2008 2007 Other

All Journal Article (28 results) (of which Peer Reviewed: 25 results) Presentation (20 results) Book (2 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] GCN5 regulates the activation of PI3K/Akt survival pathway in B cells exposed to oxidative stress via controlling gene expressions of Syk and Btk.2011

    • Author(s)
      Kikuchi, H., Kuribayashi, F., Takami, Y., Imajoh-Ohmi, S., Nakayama, T.
    • Journal Title

      Biochem. Biophys. Res. Commun. 405

      Pages: 657-661

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] GCN5 regulates the superoxide-generating system in Leukocytes via controlling gp91-phox gene expression.2011

    • Author(s)
      Kikuchi, H., Kuribayashi, F., Kiwaki, N., Takami, Y., Nakayama, T.
    • Journal Title

      J. Immunology 186

      Pages: 3015-3022

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Improved applications of the tetracycline-regulated gene depletion system.2010

    • Author(s)
      Nishijima, H., Takami, Y., Nakayama, T., Adachi, N., Shibahara, K.
    • Journal Title

      BioScience Trends 3

      Pages: 161-167

    • Related Report
      2009 Final Research Report
  • [Journal Article] Histone H1 null vertebrate cells exhibit altered nucleosome architecture.2010

    • Author(s)
      Hashimoto, H., Takami, Y., Sonoda, E., Iwasaki, T., Iwano, H., Tachibana, M., Takeda, S., Nakayama, T., Kimura, H., Shinkai, Y.
    • Journal Title

      Nucleic Acids Res. 38

      Pages: 3533-3545

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Curcumin dramatically enhances retinoic acid-induced superoxide generating activity via accumulation of p47-phox and p67-phox proteins in U937 cells.2010

    • Author(s)
      Kikuchi, H., Kuribayashi, F., Kiwaki, N., Nakayama, T.
    • Journal Title

      Biochem. Biophys. Res. Commun. 395

      Pages: 61-65

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Histone H1 null vertebrate cells exhibit altered nucleosome architecture2010

    • Author(s)
      Hashimoto H.
    • Journal Title

      Nucleic Acids Res.

      Volume: 38 Pages: 3533-3545

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] E2A participates in a fine control of pre-mature B cell apoptosis mediated by B cell receptor signaling via transcription regulations of survivin, IAP2 and caspase-8 genes.2009

    • Author(s)
      Toyonaga, K., Kikuchi, H., Yamashita, K., Nakayama, M., Chijiiwa, K., Nakayama, T.
    • Journal Title

      FEBS J. 276/5

      Pages: 1418-1428

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Lacking of Aiolos accelerates pre-mature B cell apoptosis mediated by BCR signaling through elevation in cytochrome c release.2009

    • Author(s)
      Kikuchi, H., Yamashita, K., Nakayama, M., Toyonaga, K., Tsuneyoshi, I., Takasaki, M., Nakayama, T.
    • Journal Title

      BBA-Molecular Cell Research 1793

      Pages: 1304-1314

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] E2A participates in a fine control of pre-mature B-cell apoptosis mediated by B-cell receptor signaling via transcriptional regulation of survivin, IAP2 and caspase-82009

    • Author(s)
      Toyonaga K.
    • Journal Title

      FEBS J.

      Volume: 276 Pages: 1418-1428

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lacking of Aiolos accelerates pre-mature B cell apoptosis mediated by BCR signaling through elevation in cytochrome c release2009

    • Author(s)
      Kikuchi H.
    • Journal Title

      Biochim Biophys Acta.

      Volume: 1793 Pages: 1304-1314

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Improved applications of the tetracycline-regulated gene depletion system2009

    • Author(s)
      Nishijima H.
    • Journal Title

      BioScience Trends

      Volume: 3 Pages: 161-167

    • Related Report
      2009 Annual Research Report
  • [Journal Article] E2A participates in a fine control of pre-mature B cell apoptosis mediated by B cell receptorsignaling via transcription regulations of survivin, IAP2 and caspase-8 genes.2009

    • Author(s)
      *Toyonaga, K., *Kikuchi, H., Yamashita, K., Nakayama, M., Chijiiwa, K., Nakayama, T.
    • Journal Title

      FEBS J. 276/5

      Pages: 1418-1428

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Studies on epigenetic control of B cell functions using the DT40 cell line.2009

    • Author(s)
      Kikuchi, H., Barman, H. K., Nakayama, M., Takami, Y., Nakayama, T.
    • Journal Title

      Immunogenetics Research Progress, Nova Science Publishers, Inc. NY (in press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] クロマチン構築を介したDNA複製制御2009

    • Author(s)
      高見恭成
    • Journal Title

      蛋白質・核酸・酵素 54

      Pages: 496-501

    • Related Report
      2008 Annual Research Report
  • [Journal Article] GCN5 and BCR signalling collaborate to induce pre-mature B cell apoptosis through depletion of ICAD and IAP2 and activation of caspase activities.2008

    • Author(s)
      Kikuchi, H., Nakayama, T.
    • Journal Title

      Gene 419

      Pages: 48-55

    • Related Report
      2009 Final Research Report 2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Histone acetyltransferase-1 regulates integrity of cytosolic histone H3-H4 containing complex.2008

    • Author(s)
      Barman, H.K., Takami, Y., Nishijima, H., Shibahara, K., Sanematsu, F., Nakayama, T.
    • Journal Title

      Biochem. Biophys. Res. Commun. 373

      Pages: 624-630

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Histone acetyltransferase-1 regulates integrity of cytosolic histone H3-H4 containing complex.2008

    • Author(s)
      Barman, H. K., Takami, Y., Nishijima, H., Shibahara, K., Sanematsu, F., Nakayama, T.
    • Journal Title

      Biochem. Biophys. Res. Commun. 373

      Pages: 624-630

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Studies on epigenetic control of B cell functions using the DT40 cell line2008

    • Author(s)
      Kikuchi, H., Barman, H. K., Nakayama, M., Takami, Y. and Nakayama, T.
    • Journal Title

      Immunogenetics Research Progress, Nova Science Publishers, Inc. NY (in press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Essential role of CAF-1-mediated rapid nucleosome assembly for DNA replication and cell division in vertebrate cells.2007

    • Author(s)
      Takami, Y., Ono, T., Fukagawa, T., Shibahara, K., Nakayama, T.
    • Journal Title

      Mol. Biol. Cell 18

      Pages: 129-141

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Collaborative roles of rH2AX and the Rad51 paralog Xrcc3 in homologous recombinational repair.2007

    • Author(s)
      Sonoda, E., Zhao, G.-Y., Kohzaki, M., Dhar, P.K., Kikuchi, K., Redon, C., Pilch, D.R., Bonner, W.W., Nakano, A., Watanabe, M., Nakayama, T., Takeda, S., Takami, Y.
    • Journal Title

      DNA Repair 6

      Pages: 280-292

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cleavage and cytoplasmic relocalization of histone deacetylase 3 are important for apoptosis progression.2007

    • Author(s)
      Escaffit, F., Vaute, O., Chevillard-Briet, M., Segui, B., Takami, Y., Nakayama, T., Trouche, D.
    • Journal Title

      Mol. Cell. Biol. 27

      Pages: 554-567

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] HDAC2 controls IgM H and L-chain gene expressions via EBF1, Pax5, Ikaros, Aiolos and E2A gene expressions.2007

    • Author(s)
      Nakayama, M., Suzuki, H., Yamamoto-Nagamatsu, N., Barman, H.K., Kikuchi, H., Takami, Y., Toyonaga, K., Yamashita, K., Nakayama, T.
    • Journal Title

      Genes Cells 12

      Pages: 359-373

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Histone H1 variant, H1R is involved in DNA damage response.2007

    • Author(s)
      Hashimoto, H., Sonoda, E., Takami, Y., Kimura, H., Nakayama, T., Tachibana, M., Takeda, S., Shinkai, Y.
    • Journal Title

      DNA Repair 6

      Pages: 1584-1595

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Essential role of CAF-1-mediated rapid nucleosome assembly for DNA replication and cell division in vertebrate cells2007

    • Author(s)
      Takami, Y., Ono, T., Fukagawa, T., Shibahara, K. and Nakayama, T.
    • Journal Title

      Mol. Biol. Cell 18

      Pages: 129-141

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Collaborative roles of rH2AX and the Rad51 paralog Xrcc3 in homologous recombinational repair2007

    • Author(s)
      Sonoda, E., Zhao, G.-Y., Kohzaki, M., Dhar, P. K., Kikuchi, K., Redon, C., Pilch, D. R., Bonner, W. W., Nakano, A., Watanabe, M., Nakayama, T., Takeda, S. and Takami, Y.
    • Journal Title

      DNA Repair 6

      Pages: 280-292

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cleavage and cytoplasmic relocalization of histone deacetylase 3 are important for apoptosis progression2007

    • Author(s)
      Escaffit, F., Vaute, O., Chevillard-Briet, M., Segui, B., Takami, Y., Nakayama, T. and Trouche, D.
    • Journal Title

      Mol. Cell. Biol. 27

      Pages: 554-567

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] HDAC2 controls IgM H and L-chain gene expressions via EBF1, Pax5, Ikaros, Aiolos and E2A gene expressions2007

    • Author(s)
      Nakayama, M., Suzuki, H., Yamamoto-Nagamatsu, N., Barman, H. K., Kikuchi, H., Takami, Y., Toyonaga, K., Yamashita, K. and Nakayama, T.
    • Journal Title

      Genes Cells 12

      Pages: 359-373

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Histone H1 variant, H1R is involved in DNA damage response2007

    • Author(s)
      Hashimoto, H., Sonoda, E., Takami, Y., Kimura, H., Nakayama, T., Tachibana, M., Takeda, S. and Shinkai, Y.
    • Journal Title

      DNA Repair 6

      Pages: 1584-1595

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] クルクミンによる白血球スーパーオキシド産生系誘導増強効果2010

    • Author(s)
      菊池秀彦、中山建男
    • Organizer
      第33回日本分子生物学会年会/第83回日本生化学会大会、合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-09
    • Related Report
      2009 Final Research Report
  • [Presentation] ニワトリDT40細胞を用いたミトコンドリアSirtuinsの機能解析2010

    • Author(s)
      鈴木寛之、中山建男、高見恭成
    • Organizer
      第10回日本蛋白質科学会年会
    • Place of Presentation
      札幌
    • Year and Date
      2010-06-17
    • Related Report
      2009 Final Research Report
  • [Presentation] Histone chaperone FACT is involved in efficient elongation of nascent DNA chain.2009

    • Author(s)
      阿部拓也、大沢洸司、高見恭成、多田周右、中山建男、室伏廣、堀越正美、関政幸、榎本武美
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2009-12-12
    • Related Report
      2009 Final Research Report
  • [Presentation] 転写因子AiolosによるBリンパ球アポトーシス制御機構の解析2009

    • Author(s)
      菊池秀彦、山下幸貴、中山雅美、豊永健二、中山建男
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2009-12-12
    • Related Report
      2009 Final Research Report
  • [Presentation] ノックイン変異細胞を用いたASF1/CIAの機能解析2009

    • Author(s)
      高見恭成、中山建男
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2009-12-11
    • Related Report
      2009 Final Research Report
  • [Presentation] GCN5による白血球スーパーオキシド産生系制御機構の解析2009

    • Author(s)
      木脇直美、菊池秀彦、栗林太、中山建男
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2009-12-09
    • Related Report
      2009 Final Research Report
  • [Presentation] 転写因子E2AによるBリンパ球アポトーシス制御2009

    • Author(s)
      菊池秀彦、豊永健二、山下幸貴、中山雅美、中山建男
    • Organizer
      第82回日本生化学会大会
    • Place of Presentation
      神戸
    • Year and Date
      2009-10-23
    • Related Report
      2009 Final Research Report
  • [Presentation] ノックイン変異ASF1/CIA細胞を用いたASF1の機能解析2009

    • Author(s)
      高見恭成、中山建男
    • Organizer
      第82回日本生化学会大会
    • Place of Presentation
      神戸
    • Year and Date
      2009-10-23
    • Related Report
      2009 Final Research Report
  • [Presentation] 転写因子E2AによるBリンパ球アポトーシス制御機構の解析2009

    • Author(s)
      菊池秀彦、豊永健二、山下幸貴、中山雅美、中山建男
    • Organizer
      日本分子生物学会第9回シンポジウム
    • Place of Presentation
      宮崎
    • Year and Date
      2009-05-11
    • Related Report
      2009 Final Research Report
  • [Presentation] ニワトリDT40細胞を用いたHat1の機能解析2009

    • Author(s)
      高見恭成、Hirak Kumar Barman, 中山建男
    • Organizer
      日本分子生物学会第9回シンポジウム
    • Place of Presentation
      宮崎
    • Year and Date
      2009-05-11
    • Related Report
      2009 Final Research Report
  • [Presentation] ヒストンアセチルトランスフェラーゼGCN5によるBCRシグナリング制御2008

    • Author(s)
      菊池秀彦、中山建男
    • Organizer
      第31回日本分子生物学会年会、第81回日本生化学会大会、合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2008-12-10
    • Related Report
      2009 Final Research Report
  • [Presentation] ニワトリDT40細胞を用いたhistone acethyltransferase-1(Hat1)の機能解析2008

    • Author(s)
      高見恭成、中山建男
    • Organizer
      第31回日本分子生物学会年会、第81回日本生化学会大会、合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2008-12-10
    • Related Report
      2009 Final Research Report
  • [Presentation] ヒストンアセチルトランスフェラーゼGCN5によるBCRシグナリング制御.2008

    • Author(s)
      菊池秀彦, 中山建男
    • Organizer
      第31回日本分子生物学会年会、第81回口本生化学会大会、合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2008-12-10
    • Related Report
      2008 Annual Research Report
  • [Presentation] ニワトリDT40細胞を用いたhistone acethyltransferase-1 (Hat1)の機能解析.2008

    • Author(s)
      高見恭成, 中山建男
    • Organizer
      第31回日本分子生物学会年会、第81回日本生化学会大会、合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2008-12-10
    • Related Report
      2008 Annual Research Report
  • [Presentation] ニワトリDT40細胞を用いたhistone acethyltransferase-1(Hatl)の機能解析2008

    • Author(s)
      Hirak Kumar Barman, 高見恭成、中山建男
    • Organizer
      平成20年度日本生化学会九州支部例会
    • Place of Presentation
      福岡
    • Related Report
      2009 Final Research Report
  • [Presentation] ニワトリDT40細胞を用いたhistone acethyltransferase-1 (Hatl)の機能解析.2008

    • Author(s)
      Hirak Kumar Barman, 高見恭成, 中山建男
    • Organizer
      平成20年度日本生化学会九州支部例会
    • Place of Presentation
      福岡
    • Related Report
      2008 Annual Research Report
  • [Presentation] DT40細胞を用いた遺伝子ノックアウト法によるGCN5の機能解析2007

    • Author(s)
      菊池秀彦、高見恭成、中山建男
    • Organizer
      第30回日本分子生物学会年会、第80回日本生化学会大会、合同大会
    • Place of Presentation
      横浜
    • Year and Date
      2007-12-13
    • Related Report
      2009 Final Research Report 2007 Annual Research Report
  • [Presentation] DT40細胞を用いたASF1の機能解析2007

    • Author(s)
      高見恭成、中山建男
    • Organizer
      第30回日本分子生物学会年会、第80回日本生化学会大会、合同大会
    • Place of Presentation
      横浜
    • Year and Date
      2007-12-12
    • Related Report
      2009 Final Research Report 2007 Annual Research Report
  • [Presentation] DT40細胞を用いた遺伝子ノックアウト法によるGCN5の機能解析2007

    • Author(s)
      菊池秀彦、高見恭成、中山建男
    • Organizer
      日本生化学会九州支部例会
    • Place of Presentation
      宮崎
    • Year and Date
      2007-05-20
    • Related Report
      2009 Final Research Report 2007 Annual Research Report
  • [Presentation] 脱脂粉乳を利用した新規味噌の機能性2007

    • Author(s)
      六車三治男、伊藤瑞奈、河原聡、丸山眞杉、中山建男、久寿米木一裕、菱沼毅、中村豊郎
    • Organizer
      日本生化学会九州支部例会
    • Place of Presentation
      宮崎
    • Year and Date
      2007-05-20
    • Related Report
      2007 Annual Research Report
  • [Book] Studies on epigenetic control of B cell functions using the DT40 cell line.(Advances in Genetics Research Vol.2)2010

    • Author(s)
      Kikuchi, H., Barman, H.K., Nakayama, M., Takami, Y., Nakayama, T.
    • Publisher
      Nova Science Publishers, Inc. NY
    • Related Report
      2009 Final Research Report
  • [Book] Advances in Genetics Research vol.22010

    • Author(s)
      Kikuchi H
    • Publisher
      Nova Science Publishers
    • Related Report
      2009 Annual Research Report
  • [Remarks] ホームページ等

    • URL

      http://www.med.miyazaki-u.ac.jp/2bio/index.html

    • Related Report
      2009 Final Research Report
  • [Patent(Industrial Property Rights)] レチノイン酸効果増強剤およびこれを用いたリンパ腫治療剤キット、並びに、活性酸素産生促進剤およびこれを用いた免疫賦活剤2010

    • Inventor(s)
      菊池秀彦、木脇直美、中山建男
    • Industrial Property Rights Holder
      宮崎大学
    • Industrial Property Number
      2010-059734
    • Filing Date
      2010-03-16
    • Related Report
      2009 Final Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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