Core histone modifications change the higher order of DNA structurec resulting in its biological output

• Project/Area Number: 15390098
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Nagasaki University
• Principal Investigator: ITO Takashi Nagasaki University, Graduate School of Biomedical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (90306275)
• Co-Investigator(Kenkyū-buntansha): IKEHARA Tsuyoshi Nagasaki University, Graduate School of Biomedical Sciences, Assistant Professor, 大学院・医歯薬学総合研究科, 講師 (90359951) ; NAKAGAWA Takeya Nagasaki University, Graduate School of Biomedical Sciences, Research Associate, 大学院・医歯薬学総合研究科, 助手 (50363502) ; YASUI Kiyoshi Nagasaki University, Graduate School of Biomedical Sciences, Research Associate, 大学院・医歯薬学総合研究科, 助手 (50372777)
• Project Period (FY): 2003 – 2004
• Project Status: Completed(Fiscal Year 2004)
• Budget Amount: ¥14,700,000 (Direct Cost : ¥14,700,000); Fiscal Year 2004 : ¥5,200,000 (Direct Cost : ¥5,200,000); Fiscal Year 2003 : ¥9,500,000 (Direct Cost : ¥9,500,000)
• Keywords: histone / acetylation / phosphorylation / nucleosome / chromatin / transcription

Research Abstract

In the eukaryotic nucleus, DNA exists as a nucleoprotein complex termed chromatin. The work is based on the hypothesis that chromatin dynamics and structure are an integral component of the analysis of DNA-dependent processes. Posttranslational histone modifications are important for the regulation of many biological phenomena. In this project, we clafified that a precise role for histone acetylation, namely to alter the structure of nucleosomes and facilitate the loss of H2A-H2B dimmers that have been previously remodeled by the action of ATP-dependent chromatin remodeling complexes. We also clarified that transcription from chromatin templates is ordered and sequential, with precise timing and roles for ATP-dependent chromatin remodeling, subsequent histone acetylation and alterations in nucleosome structure. In addition we found that histone H2A is phosphorylated by unique kinase. We found that NHK-1-catalyzed phosphorylation of a conserved serine/threonine residue in H2A is a new component of the histone code which might be related to cell cycle progression.

Research Products

• [Journal Article] Nucleosomal histone kinase-1 phosphorylates H2A Thr 119 during mitosis in the early Drosophila embryo. (2004)
  • Author(s): Aihara, H., Nakagawa, T.et al.
  • Journal Title: Genes Dev 18 Pages : 877-888
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] A Pitfall in Diagnosis of Human Prion Diseases Using Detection of Protease-resistant Prion Protein in Urine : CONTAMINATION WITH BACTERIAL OUTER MEMBRANE PROTEINS. (2004)
  • Author(s): Furukawa, H., Doh-Ura, K et al.
  • Journal Title: J Biol Chem 279 Pages : 23661-23667
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Isoflavones stimulate estrogen receptor-mediated core histone acetylation. (2004)
  • Author(s): Hong, T., Nakagawa, T et al.
  • Journal Title: Biochem Biophys Res Commun 317 Pages : 259-264
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Identification of ser-386 of interferon regulatory factor 3 as critical target for inducible phosphorylation that determines activation. (2004)
  • Author(s): Mori, M., Yoneyama, M., Ito, T.et al.
  • Journal Title: J Biol Chem 279 Pages : 9698-9702
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Nucleosomal histone kinase-1 phosphorylates H2A Thr 119 during mitosis in the early Drosophila embryo. (2004)
  • Author(s): Aihara, H., Nakagawa, T., Yasui, K., Ohta, T., Hirose, S., Dhomae, N., Takio, K., Kaneko, M., Takeshima, Y., Muramatsu, M., Ito, T.
  • Journal Title: Genes Dev 18 Pages : 877-888
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A Pitfall in Diagnosis of Human Prion Diseases Using Detection of Protease-resistant Prion Protein in Urine : CONTAMINATION WITH BACTERIAL OUTER MEMBRANE PROTEINS. (2004)
  • Author(s): Furukawa, H., Doh-Ura, K., Okuwaki, R., Shirabe, S., Yamamoto, K., Udono, H., Ito, T., Katamine, S., Niwa, M.
  • Journal Title: J Biol Chem 279 Pages : 23661-23667
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Isoflavones stimulate estrogen receptor-mediated core histone acetylation. (2004)
  • Author(s): Hong, T., Nakagawa, T., Pan, W., Kim, M.Y., Kraus, W.L, Ikehara, T., Yasui, K., Aihara, H., Takebe, M., Muramatsu, M., Ito, T.
  • Journal Title: Biochem Biophys Res Commun 317 Pages : 259-264
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Identification of ser-386 of interferon regulatory factor 3 as critical target for inducible phosphorylation that determines activation. (2004)
  • Author(s): Mori, M., Yoneyama, M., Ito, T., Takahashi, K., Inagaki, F., Fujita, T.
  • Journal Title: J Biol Chem 279 Pages : 9698-9702
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Nucleosomal histone kinase-1 phosphorylates H2A Thr 119 during mitosis in the early Drosophila embryo. (2004)
  • Author(s): Aihara, H., Nakagawa, T., Yasui, K., Ohta, T., Hirose, S., Dhomae, N., Takio, K., Kaneko, M., Takeshima, Y., Muramatsu, M., Ito, T
  • Journal Title: Genes Dev 18 Pages : 877-888
• [Journal Article] A Pitfall in Diagnosis of Human Prion Diseases Using Detection of Protease-resistant Prion Protein in Urine : CONTAMINATION WITH BACTERIAL OUTER MEMBRANE PROTEIN (2004)
  • Author(s): Furukawa, H., Doh-Uta, K., Okuwaki, R., Shirabe, S., Yamamoto, K, Udono, H., Ito, T., Katamine, S., Niwa, M.
  • Journal Title: J Biol Chem 279 Pages : 23661-23667
• [Journal Article] Isfolavones stimulate estrogen receptor-mediated core histone acetylation (2004)
  • Author(s): Hong, T., Nakagawa, T., Pan, W., Kim, M.Y., Kraus, W.L., Ikehara, T., Yasui, K., Aihara, H., Takebe, M., Muramatsu, M., Ito, T.
  • Journal Title: Biochem Biophys Res Commun 317 Pages : 259-264
• [Journal Article] Identification of ser-386 of interferon regulatory factor 3 as critical target for inducible phosphorylation that determines activation. (2004)
  • Author(s): Mori., M., Yoneyama., M., Ito., T., Takahashi., K., Inagaki., F., Fujita., T.
  • Journal Title: J Biol Chem 279 Pages : 9698-9702
• [Journal Article] The chromatin-remodeling complex WINAC targets a nuclear receptor to promoters and is impaired in Williams syndrome. (2003)
  • Author(s): Kitagawa, H., Fujiki, R., Yoshimura, K., Mezaki, Y., Uematsu, Y., Matsui, D., Ogawa, S., Unno, K., Okubo, M., Tokita, A., Nakagawa, T., Ito, T.et al.
  • Journal Title: Cell 113 Pages : 905-917
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Nucleosome assembly and remodeling (2003)
  • Author(s): Ito, T
  • Journal Title: Curr Top Microbiol Immunol 274 Pages : 1-22
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] 蛋白質複合体によるクロマチン構造変換 (2003)
  • Author(s): 伊藤 敬
  • Journal Title: 実験医学 21 Pages : 1398-1401
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] クロマチンの形成と再構築 (2003)
  • Author(s): 安井 潔, 伊藤 敬
  • Journal Title: 実験医学 21 Pages : 1402-1407
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] シグナル伝達とクロマチン制御 (2003)
  • Author(s): 中川 武弥, 伊藤 敬
  • Journal Title: 蛋白質核酸酵素 48 Pages : 2234-2240
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] The chromatin-remodeling complex WINAC targets a nuclear receptor to promoters and is impaired in Williams syndrome. (2003)
  • Author(s): Kitagawa, H., Fujiki, R., Yoshimura, K., Mezaki, Y., Uematsu, Y., Matsui, D., Ogawa, S., Unno, K., Okubo, M., Tokita, A., Nakagawa, T., Ito, T., Ishimi, Y., Nagasawa, H., Matsumoto, T., Yanagisawa, J., Kato, S.
  • Journal Title: Cell 113 Pages : 905-917
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Nucleosome assembly and remodeling. (2003)
  • Author(s): Ito, T.
  • Journal Title: Curr Top Microbiol Immunol 274 Pages : 1-22
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Protein complexes that affect chromatin structure (2003)
  • Author(s): Ito, T.
  • Journal Title: Jikkenigaku 21 Pages : 1398-1401
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Chromatin assembly and remodeling (2003)
  • Author(s): Yasui, K., Ito, T.
  • Journal Title: Jikkenigaku 21 Pages : 1402-1407
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Signal transduction and chromatin (2003)
  • Author(s): Nakagawa, T., Ito, T.
  • Journal Title: Tanpakushitu Kakusan Koso 48 Pages : 2234-2240
  • Description: 「研究成果報告書概要(欧文)」より
• [Book] ショウジョウバエ胚抽出液によるクロマチン形成法 (2004)
  • Author(s): 分担執筆 伊藤 敬
  • Total Pages: 231
  • Publisher: 羊土社
  • Description: 「研究成果報告書概要(和文)」より
• [Book] クロマチン染色体実験プロトコール ショウジョウバエ胚抽出液によるクロマチン形成法 (2004)
  • Author(s): 押村光雄, 平岡泰 編, 分担執筆 伊藤 敬
• [Book] 新ラボマニュアル遺伝子工学 (2003)
  • Author(s): 分担執筆 池原強, 中川武弥, 伊藤 敬
  • Total Pages: 291
  • Publisher: 丸善株式会社
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Mori, M., Yoneyama, M., Ito, T.et al.: "Identification of ser-386 of interferon regulatory factor 3 as critical target for inducible phosphorylation that determines activation"J Biol Chem. 279. 9698-9702 (2004)
• [Publications] Kitagawa, H., Fujiki, R., Yoshimura, K., Mezaki, Y., Uematsu, Y., Matsui, D., Ogawa, S., Unno, K., Okubo, M., Tokita, A., Nakagawa, T., Ito, T.et al.: "The chromatin-remodeling complex WINAC targets a nuclear receptor to promoters and is impaired in Williams syndrome"Cell. 113. 905-917 (2003)
• [Publications] Ito, T: "Nucleosome assembly and remodeling"Curr Top Microbiol Immunol. 274. 1-22 (2003)