Structural and functional studies for nuclear macromolecular complexes

2012 Fiscal Year Final Research Report

• Project Area: The physicochemical field for genetic activities
• Project/Area Number: 20114005
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Waseda University
• Principal Investigator: KURUMIZAKA Hitoshi 早稲田大学, 理工学術院, 教授 (80300870)
• Project Period (FY): 2008 – 2012
• Keywords: 染色体 / 遺伝子 / 蛋白質 / 高次構造 / 細胞核

Research Abstract

Nucleosome is the primary building block for chromatin, which packages huge genomic DNA. Histones are protein components of the nucleosome, and several non-allelic histone variants have been identified in higher eukaryotes. In this study, we determined the crystal structures of human nucleosomes, containing one of each histone H3 variants, H3.1, H3.2, H3.3, H3T, or CENP-A. We also identified novel histone variants, which promote nucleosome assembly. These findings provide important information to understand the chromatin architecture with functional nucleosome dynamics.

Research Products

• [Journal Article] Vertebrate Spt2 is a novel nucleolar histone chaperone that assists in ribosomal DNA transcription (2013)
  • Author(s): Osakabe A., Tachiwana H., Takaku M., Hori T., Obuse C., Kimura H., Fukagawa T., Kurumizaka H
  • Journal Title: J. Cell Sci Volume: 126 Pages: 1323-1332
  • Peer Reviewed
• [Journal Article] Purification and characterization of the fission yeast telomere clustering factors, Bqt1 and Bqt2 (2013)
  • Author(s): Ichikawa Y., Kagawa W., Saito K., Chikashige Y., Haraguchi T., Hiraoka Y., Kurumizaka H
  • Journal Title: Prot. Exp. Purif Volume: 88 Pages: 207-213
  • Peer Reviewed
• [Journal Article] Gas-Phase Structure of the Histone Multimers Characterized by Ion Mobility Mass Spectrometry and Molecular Dynamics Simulation (2013)
  • Author(s): Saikusa K., Fuchigami S., Takahashi K., Asano Y., Nagadoi A., Tachiwana H., Kurumizaka H., Ikeguchi M., Nishimura Y., Akashi, S
  • Journal Title: Anal. Chem Volume: 85 Pages: 4165-4171
  • Peer Reviewed
• [Journal Article] Current progress on structural studies of nucleosomes containing histone H3 variants (2013)
  • Author(s): Kurumizaka H., Horikoshi N., Tachiwana H., Kagawa W
  • Journal Title: Curr. Opin. Struct. Biol Volume: 23 Pages: 109-115
  • Peer Reviewed
• [Journal Article] Nap1 regulates proper CENP-B binding to nucleosomes (2013)
  • Author(s): Tachiwana H., Miya Y., Shono N., Ohzeki J., Osakabe A., Otake K., Larionov V., Earnshaw W.C., Kimura H., Masumoto H., Kurumizaka H
  • Journal Title: Nucleic Acids Res Volume: 5 Pages: 2869-2880
  • Peer Reviewed
• [Journal Article] Histone chaperone activity of Fanconi anemia proteins, FANCD2 and FANCI, is required for DNA crosslink repair (2012)
  • Author(s): Sato K., Ishiai M., Toda K., Furukoshi S., Osakabe A., Tachiwana H., Takizawa Y., Kagawa W., Kitao H., Dohmae N., Obuse C., Kimura H., Takata M., Kurumizaka H
  • Journal Title: EMBO J Volume: 31 Pages: 3524-3536
  • Peer Reviewed
• [Journal Article] Chd2 interacts with H3.3 to determine myogenic cell fate (2012)
  • Author(s): Harada A., Okada S., Odawara J Kumamaru H., Saiwai H., Konno D., Yoshimi T., Yoshimura S., Tachibana T., Tsubota T., Kurumizaka H., Akashi K., Imbalzano A.N., Ohkawa Y
  • Journal Title: EMBO J Volume: 31 Pages: 2994-3007
  • Peer Reviewed
• [Journal Article] Structural analysis of the hexasome, lacking one histone H2A/H2B dimer from the conventional nucleosome (2012)
  • Author(s): Arimura Y., Tachiwana H., Oda T., Sato M., Kurumizaka H
  • Journal Title: Biochemistry Volume: 51 Pages: 3302-3309
  • Peer Reviewed
• [Journal Article] Comparison between the CENP-A and histone H3 structures in nucleosomes (2012)
  • Author(s): Tachiwana H., Kagawa W., Kurumizaka H
  • Journal Title: Nucleus Volume: 3 Pages: 1-6
  • Peer Reviewed
• [Journal Article] Structural basis for the DNA binding activity of the bacterial β-propeller protein YncE (2011)
  • Author(s): Kagawa W., Sagawa T., Niki H., Kurumizaka H
  • Journal Title: Acta Cryst Volume: D67 Pages: 1045-1053
  • Peer Reviewed
• [Journal Article] Comprehensive structural analysis of mutant nucleosomes containing lysine to glutamine (KQ) substitutions in the H3 and H4 histone-fold domains (2011)
  • Author(s): Iwasaki W., Tachiwana H., Kawaguchi K., Shibata T., Kagawa W., Kurumizaka H
  • Journal Title: Biochemistry Volume: 50 Pages: 7822-7832
  • Peer Reviewed
• [Journal Article] Crystal structure of the human centromeric nucleosome containing CENP-A (2011)
  • Author(s): Tachiwana H., Kagawa W., Shiga T., Osakabe A., Miya Y., Saito K., Hayashi-Takanaka Y., Oda T., Sato M., Park S.-Y., Kimura H., Kurumizaka H
  • Journal Title: Nature Volume: 476 Pages: 232-235
  • Peer Reviewed
• [Journal Article] Structures of human nucleosomes containing major histone H3 variants (2011)
  • Author(s): Tachiwana H., Osakabe A., Shiga T., Miya Y., Kimura H., Kagawa W., Kurumizaka H
  • Journal Title: Acta Cryst Volume: D67 Pages: 578-583
  • Peer Reviewed
• [Journal Article] Tracking epigenetic histone modifications in single cells using Fab-based live endogenous modification labeling (2011)
  • Author(s): Hayashi-Takanaka Y., Yamagata K., Wakayama T., Stasevich T.J., Kainuma T., Tsurimoto T., Tachibana M., Shinkai Y., Kurumizaka H., Nozaki N., Kimura H
  • Journal Title: Nucleic Acids Res Volume: 39 Pages: 6475-6488
  • Peer Reviewed
• [Journal Article] Structural and biochemical analyses of the human PAD4 variant encoded by a functional haplotype gene (2011)
  • Author(s): Horikoshi N., Tachiwana H., Saito K., Osakabe A., Sato M., Yamada M., Akashi S., Nishimura Y., Kagawa W., Kurumizaka H
  • Journal Title: Acta Cryst Volume: D67 Pages: 112-118
  • Peer Reviewed
• [Journal Article] Structural basis of instability of the nucleosome containing a testis-specific histone variant, human H3T (2010)
  • Author(s): Tachiwana H., Kagawa W., Osakabe A., Kawaguchi K., Shiga T., Hayashi-Takanaka, Y, Kimura, H., and Kurumizaka H
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 107 Pages: 10454-10459
  • Peer Reviewed
• [Journal Article] Deimination stabilizes histone H2A/H2B dimers as revealed by electrospray ionization mass spectrometry (2010)
  • Author(s): Shimoyama S., Nagadoi A., Tachiwana H., Yamada M., Sato M., Kurumizaka H., Nishimura Y., Akashi S
  • Journal Title: J. Mass Spectrom Volume: 45 Pages: 900-908
  • Peer Reviewed
• [Journal Article] Nucleosome formation activity of human sNASP (2010)
  • Author(s): Osakabe A., Tachiwana H., Matsunaga T., Shiga T., Nozawa R., Obuse C., Kurumizaka H
  • Journal Title: J. Biol. Chem Volume: 285 Pages: 11913-11921
  • Peer Reviewed
• [Journal Article] Biochemical analysis of the human EVL domains in homologous recombination (2009)
  • Author(s): Takaku M., Machida S., Nakayama S., Takahashi D., Kurumizaka H
  • Journal Title: FEBS J Volume: 276 Pages: 5841-5848
  • Peer Reviewed
• [Journal Article] Human PSF binds to RAD51 and modulates its homologous-pairing and strand-exchange activities (2009)
  • Author(s): Morozumi Y., Takizawa Y., Takaku M., Kurumizaka H
  • Journal Title: Nucleic Acids Res Volume: 37 Pages: 4296-4307
  • Peer Reviewed
• [Journal Article] The ATR-Chk1 pathway plays a role in the generation of centrosome aberrations induced by Rad51C dysfunction (2009)
  • Author(s): Katsura M., Tsuruga T., Date O., Yoshihara T., Ishida M., Tomoda Y., Okajima M., Takaku M., Kurumizaka H., Kinomura A., Mishima H., Miyagawa K
  • Journal Title: Nucleic Acids Res Volume: 37 Pages: 3959-3968
  • Peer Reviewed
• [Journal Article] Recombination activator function of the novel RAD51- and RAD51B-binding protein, Human EVL (2009)
  • Author(s): Takaku M., Machida S., Hosoya N., Nakayama S., Takizawa Y., Sakane I., Shibata T., Miyagawa K., Kurumizaka H
  • Journal Title: J. Biol. Chem Volume: 284 Pages: 14326-14336
  • Peer Reviewed
• [Journal Article] DIDS, a chemical compound that inhibits RAD51-mediated homologous pairing and strand exchange (2009)
  • Author(s): Ishida T., Takizawa Y., Kainuma T., Inoue J., Mikawa T., Shibata T., Suzuki H., Tashiro S., Kurumizaka H
  • Journal Title: Nucleic Acids Res Volume: 37 Pages: 3367-3376
  • Peer Reviewed
• [Journal Article] c-ABL tyrosine kinase stabilizes RAD51 chromatin association (2009)
  • Author(s): Shimizu H., Popova M., Fleury F., Kobayashi M., Hayashi N., Sakane I., Kurumizaka H., Venkitaraman A.R., Takahashi M., Yamamoto KI
  • Journal Title: Biochem. Biophys Res. Commun Volume: 382 Pages: 286-291
  • Peer Reviewed
• [Journal Article] Biochemical analysis of the human DMC1-I37N polymorphism (2009)
  • Author(s): Hikiba J., Takizawa Y., Ikawa S., Shibata T., Kurumizaka H
  • Journal Title: FEBS J Volume: 276 Pages: 457-465
  • Peer Reviewed
• [Journal Article] Structural analysis of the human Rad51 protein-DNA complex filament by tryptophan fluorescence scanning analysis: transmission of allosteric effects between ATP binding and DNA binding (2008)
  • Author(s): Renodon-Corniere A. Takizawa Y., Conilleau1 S., Tran V., Iwai S., Kurumizaka H., Takahashi M
  • Journal Title: J. Mol. Biol Volume: 383 Pages: 575-578
  • Peer Reviewed
• [Journal Article] Biochemical analysis of the N-terminal domain of human RAD54B (2008)
  • Author(s): Sarai N., Kagawa W., Fujikawa N., Saito K., Hikiba J., Tanaka K., Miyagawa K., Kurumizaka H., Yokoayama S
  • Journal Title: Nucleic Acids Res Volume: 36 Pages: 5441-5450
  • Peer Reviewed
• [Journal Article] Identification of a second DNA binding site in the human Rad52 protein (2008)
  • Author(s): Kagawa W., Kagawa A., Saito K., Ikawa S., Shibata T., Kurumizaka H., Yokoyama S
  • Journal Title: J. Biol. Chem Volume: 283 Pages: 24264-24273
  • Peer Reviewed
• [Journal Article] Filament formation and robust strand exchange activities of the rice DMC1A and DMC1B proteins (2008)
  • Author(s): Sakane I., Kamataki C., Takizawa Y., Nakashima M., Toki S., Ichikawa H., Ikawa S., Shibata T., Kurumizaka H
  • Journal Title: Nucleic Acids Res Volume: 36 Pages: 4266-4276
  • Peer Reviewed
• [Journal Article] Structural and functional analyses of the DMC1-M200V polymorphism found in the human population (2008)
  • Author(s): Hikiba J., Hirota K., Kagawa W., Ikawa S., Kinebuchi T., Sakane I., Takizawa Y., Yokoyama S., Mandon-Pepin B., Nicolas A., Shibata T., Ohta K., Kurumizaka H
  • Journal Title: Nucleic Acids Res Volume: 36 Pages: 4181-4190
  • Peer Reviewed
• [Journal Article] Inhibition of filament formation of human Rad51 protein by a small peptide derived from the BRC-motif of the BRCA2 protein (2008)
  • Author(s): Nomme J., Takizawa Y., Martinez S., Renodon-Corniere A., Fleury F., Weigel P., Yamamoto K., Kurumizaka H., Takahashi M
  • Journal Title: Genes Cells Volume: 13 Pages: 471-481
  • Peer Reviewed
• [Journal Article] Nucleosome formation with the testis-specific histone H3 variant, H3t, by human nucleosome assembly proteins in vitro (2008)
  • Author(s): Tachiwana H., Osakabe A., Kimura H., Kurumizaka H
  • Journal Title: Nucleic Acids Res Volume: 36 Pages: 2208-2218
  • Peer Reviewed
• [Presentation] 動的なヌクレオソーム構造によるクロマチン制御機構 (2013)
  • Author(s): 胡桃坂仁志
  • Organizer: 第4回中性子小角散乱解析法研究会
  • Place of Presentation: 東京
  • Year and Date: 20130300
• [Presentation] ヒストンバリアントによるヌクレオソームの構造多様性 (2013)
  • Author(s): 胡桃坂仁志
  • Organizer: 第1回ヒストンバリアント研究会
  • Place of Presentation: 福岡
  • Year and Date: 20130300
• [Presentation] ヒストンとヒストンシャペロンによるクロマチンダイナミクス機構 (2012)
  • Author(s): 胡桃坂仁志
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡
  • Year and Date: 20121200
• [Presentation] エピゲノムを担う機能的クロマチンにおけるヒストンバリアントの構造的役割 (2012)
  • Author(s): 胡桃坂仁志
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
  • Year and Date: 20121200
• [Presentation] Nucleosome structures during transcription and DNA repair (2012)
  • Author(s): Kurumizaka H
  • Organizer: The 8th 3R Symposium
  • Place of Presentation: 兵庫
  • Year and Date: 20121100
• [Presentation] Structural basis for the functional versatility of human nucleosomes containing histone variants (2012)
  • Author(s): Kurumizaka H
  • Organizer: Telluride Workshop on Chromatin Structure and Dynamics
  • Place of Presentation: Telluride、USA
  • Year and Date: 20120800
• [Presentation] Structural basis for formation of functional chromatin architecture (2011)
  • Author(s): Kurumizaka H
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 神奈川
  • Year and Date: 20111200
• [Presentation] INSTABILITY AND STRUCTURAL PROPERTY OF A HUMAN TESTIS-SPECIFIC HISTONE H3T NUCLEOSOME (2011)
  • Author(s): Kurumizaka H
  • Organizer: World Congress on Reproductive Biology
  • Place of Presentation: Cairns、Australia
  • Year and Date: 20111000
• [Presentation] ヒストンバリアントによるヌクレオソーム構造の多様性と機能発現 (2011)
  • Author(s): 胡桃坂仁志、立和名博昭、香川亘、志賀達也、越阪部晃永、堀越直樹、有村泰宏、宮優太、松本亮平
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 20110900
• [Presentation] Structural similarity and versatility of the human nucleosomes (2011)
  • Author(s): Kurumizaka H., Tachiwana H., Kagawa W., Osakae A., Shiga T., Miya Y., Matsumoto R
  • Organizer: EMBO Conference Series Chromatin and Epigenetics
  • Place of Presentation: Heidelberg、Germany
  • Year and Date: 20110600
• [Presentation] ヒストンバリアントを含むヌクレオソームの構造多様性と機能 (2010)
  • Author(s): 胡桃坂仁志、立和名博昭、香川亘、志賀達也、越阪部晃永、林(高中)陽子、木村宏
  • Organizer: Biochemistry and Molecular Biology 2010
  • Place of Presentation: 兵庫
  • Year and Date: 20101200
• [Presentation] ヌクレオソームの立体構造からみたエピジェネティクスの分子機構 (2010)
  • Author(s): 胡桃坂仁志
  • Organizer: 第21回フォーラム・イン・ドージン エピジェネティクスによる細胞のメタモルフォーゼ
  • Place of Presentation: 熊本
  • Year and Date: 20101100
• [Presentation] クロマチンの基盤構造であるヌクレオソームの機能・構造解析 (2009)
  • Author(s): 胡桃坂仁志、立和名博昭、越阪部晃永、川口紘一郎、香川亘
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 神奈川
  • Year and Date: 20091200
• [Presentation] Stractual and functional analyses of the nucleosome containing a testis-specific histone variant, human H3T (2009)
  • Author(s): Kurumizaka H
  • Organizer: The EMBO Conference on Meiosis (1st)
  • Place of Presentation: Avignon、France
  • Year and Date: 20090900
• [Presentation] リコンビナントヒストンによるin vitroヌクレオソーム再構築 (2009)
  • Author(s): 胡桃坂仁志
  • Organizer: 第8回核ダイナミクス研究会
  • Place of Presentation: 静岡
  • Year and Date: 20090600
• [Presentation] ゲノム配列情報の安定維持と多様化に重要な相同組換え因子群の機能解析 (2008)
  • Author(s): 胡桃坂仁志
  • Organizer: Biochemistry and Molecular Biology 2008
  • Place of Presentation: 兵庫
  • Year and Date: 20081200
• [Book] SPring-8 Research Frontiers (2011)
  • Author(s): Tachiwana H., Kagawa W., Kurumizaka H
  • Publisher: ROKKO Publishing & Sale Co.
• [Book] 実験医学別冊 目的別で選べる核酸実験の原理とプロトコール (2011)
  • Author(s): 平尾一郎、胡桃坂仁志 編
  • Publisher: 羊土社
• [Book] 最新医学 第65巻/6月増刊号 発がん防御に重要な相同組換えの分子機構 (2010)
  • Author(s): 齊藤健吾、香川亘、胡桃坂仁志
  • Publisher: 最新医学社