Post-translational histnoe modification and chromatin strucure

• Project/Area Number: 17054032
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Nagasaki University
• Principal Investigator: ITO Takashi Nagasaki University, 大学院・医歯薬学総合研究科, 教授 (90306275)
• Co-Investigator(Kenkyū-buntansha): NAKAGAWA Takeya 長崎大学, 大学院・医歯薬学総合研究科, 助教 (50363502) ; NANABA Yasuaki 長崎大学, 大学院・医歯薬学総合研究科, 助教 (90444869) ; MIZUSAKI Hirofumi 長崎大学, 大学院・医歯薬学総合研究科, 助教 (40467957) ; 沖 昌也 長崎大学, 大学院医歯薬学総合研究科, 助手 (60420626) ; 安井 潔 長崎大学, 大学院医歯薬学総合研究科, 助手 (50372777)
• Project Period (FY): 2005 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥108,200,000 (Direct Cost: ¥108,200,000); Fiscal Year 2009: ¥21,600,000 (Direct Cost: ¥21,600,000); Fiscal Year 2008: ¥21,900,000 (Direct Cost: ¥21,900,000); Fiscal Year 2007: ¥22,100,000 (Direct Cost: ¥22,100,000); Fiscal Year 2006: ¥22,300,000 (Direct Cost: ¥22,300,000); Fiscal Year 2005: ¥20,300,000 (Direct Cost: ¥20,300,000)
• Keywords: DNA高次構浩 / アセチル化 / エピジェネティクス / クロマチン / ヌクレオソーム / ヒストン / ユビキチン化 / リン酸化 / 遺伝子転写 / DNA高次構造 / 肝再生 / 脱ユビキチン化 / クロストーク / 転写開始 / 翻訳後修飾 / 再構築

Research Abstract

In the eukaryotic nucleus, genomic DNA interacts with numerous proteins to form chromatin. Packaging of the template into chromatin appears to affect all stages of transcription, including initiation and elongation. Diverse histone modifications, such as acetylation, methylation and ubiquitylation have been linked to the regulation of cellular activities such as transcription, repair and replication. In this project we clarified unique histone deubiquitylase USP21. USP21 hydrolyzes isopeptide bond between histone H2A and ubiquitin. We identified that USP21 activate transcription through histone modification cascade that connects deubiquitylation of ubiquitylkated histone H2A, histone H3 K4 methylation and subsequent transcriptional activation.

Research Products

• [Journal Article] A histone chaperone, DEK, transcriptionally coactivates a nuclear receptor. (2010)
  • Author(s): Sawatsubashi, S., Murata, T., Lim, J., Fujiki, R., Ito, S., Suzuki, E., Tanabe, M., Zhao, Y., Kimura, S., Fujiyama, S., Ueda, T., Umetsu, D., Ito, T., Takeyama, K., Kato, S.
  • Journal Title: Genes Dev 24 Pages: 159-170
• [Journal Article] A histne chaperone, DEK, transcriptionally coactivates a nuclear receptor. (2010)
  • Author(s): Sawatsubashi, S., Murata, T., Lim, J., Fujiki, R., Ito, S., Suzuki, E., Tanabe, M., Zhao, Y., Kimura, S., Fujiyama, S., Ueda, T., Umetsu, D., Ito, T., Takeyama, K., Kato, S.
  • Journal Title: Genes Dev 24 Pages: 159-170
  • Peer Reviewed
• [Journal Article] ヒストンH2Aのユビキチン化と遺伝子転写抑制 (2010)
  • Author(s): 伊藤敬
  • Journal Title: 生化学 Vol 82 Pages: 232-236
  • NAID: 10026300867
• [Journal Article] Deubiquitylation of histone H2A activates transcriptional initiation via trans-histone cross-talk with H3K4 di- and trimethylation. (2008)
  • Author(s): Nakagawa, T., Kajitani, T., Togo, S., Masuko, N., Ohdan, H., Hishikawa, Y., Koji, T., Matsuyama, T., Ikura, T., Muramatsu, M., Ito, T.
  • Journal Title: Genes Dev 22(1) Pages: 37-49
• [Journal Article] 肝臓再生とユビキチン化ヒストンH2Aによる遺伝子転写制御 (2008)
  • Author(s): 伊藤敬
  • Journal Title: 実験医学 26 Pages: 1347-1352
• [Journal Article] Deubiquitylation of histone H2A activates transcriptional initiation via trans-histone cross-talk with H3K4 di-and trimethylation. (2008)
  • Author(s): Nakagawa, T., Kajitani, T., Togo, S., Masuko, N., Ohdan, H., Hishikawa, Y., Koji, T., Matsuyama, T., Ikura, T., Muramatsu, M., and Ito, T.
  • Journal Title: Genes Dev 22 Pages: 37-49
  • Peer Reviewed
• [Journal Article] DNA damage-dependent acetylation and ubiquitination of H2AX enhances chromatin dynamics. (2007)
  • Author(s): Ikura, T., Tashiro, S., Kakino, A., Shima, H., Jacob, N., Amunugama, R., Yoder, K., Izumi, S., Kuraoka, I., Tanaka, K., Kimura, H., Ikura, M., Nishikubo, S., Ito, T., Muto, A., Miyagawa, K., Takeda, S., Fishel, R., Igarashi, K., Kamiya, K.
  • Journal Title: Mol Cell Biol 27(20) Pages: 7028-7040
• [Journal Article] Concerted action of Aurora B, Polo and NHK-1 kinases in centromere-specific histone 2A phosphorylation. (2007)
  • Author(s): Brittle, A.L., Nanba, Y., Ito, T., Ohkura, H.
  • Journal Title: Exp Cell Res 313(13) Pages: 2780-2785
• [Journal Article] Role of histone modification in chromatin dynamics. (2007)
  • Author(s): Ito, T.
  • Journal Title: J Biochem 141(5) Pages: 609-614
  • NAID: 10020098988
• [Journal Article] Role of histone phosphorylation in chromatin dynamics and its implications in diseases. (2007)
  • Author(s): Oki, M., Aihara, H., Ito, T.
  • Journal Title: Subcell Biochem 41 Pages: 319-336
• [Journal Article] DNA damage-dependent acetylation and ubiquitination of H2AX enhances chromatin dynamics. (2007)
  • Author(s): Ikura, T., Tashiro, S., Kakino, A., Shima, H., Jacob, N., Amunugama, R., Yoder, K., Izumi, S., Kuraoka, I., Tanaka, K., Kimura, H., Ikura, M., Nishikubo, S., Ito, T., Muto, A., Miyagawa, K., Takeda, S., Fishel, R., Igarashi, K., and Kamiya, K.
  • Journal Title: Mol Cell Biol 27 Pages: 7028-7040
  • Peer Reviewed
• [Journal Article] Concerted action of Aurora B, Polo and NHK-1 kinases in centromere-specific histone 2A phosphorylation. (2007)
  • Author(s): Brittle, A. L., Nanba, Y., Ito, T., and Ohkura, H.
  • Journal Title: Exp Cell Res 313 Pages: 2780-2785
  • Peer Reviewed
• [Journal Article] Aminopeptidase N (proteobacteria alanyl aminopeptidase) from Escherichia coli: Crystal structure and conformational change of the methionine 260 residue involved in substrate recognition. (2006)
  • Author(s): Ito, K., Nakajima, Y., Onohara, Y., Takeo, M., Nakashima, K., Matsubara, F., Ito, T., Yoshimoto, T.
  • Journal Title: J Biol Chem 281(44) Pages: 33664-33676
• [Journal Article] Regulation of histone acetylation and nucleosome assembly by transcription factor JDP2. (2006)
  • Author(s): Jin, C., Kato, K., Chimura, T., Yamasaki, T., Nakade, K., Murata, T., Li, H., Pan, J., Zhao, M., Sun, K., Chiu, R., Ito, T., Nagata, K., Horikoshi, M., Yokoyama, K.K.
  • Journal Title: Nature Structural & Molecular Biology 13(4) Pages: 331-338
• [Journal Article] Crystal structure and mechanism of tripeptidyl activity of prolyl tripeptidyl aminopeptidase from Porphyromonas gingivalis. (2006)
  • Author(s): Ito, K., Nakajima, Y., Xu, Y., Yamada, N., Onohara, Y., Ito, T., Matsubara, F., Kabashima, T., Nakayama, K., Yoshimoto, T.
  • Journal Title: J Mol Biol 362(2) Pages: 228-240
• [Journal Article] The conserved kinase NHK-1 is essential for mitotic progression and unifying acentrosomal meiotic spindles in Drosophila melanogaster. (2006)
  • Author(s): Cullen, C.F., A.L. Brittle, T. Ito, H. Ohkura.
  • Journal Title: J Cell Biol 171 Pages: 593-602
• [Journal Article] Aminopeptidase N (proteobacteria alanyl aminopeptidase) from Escherichia coli : Crystal structure and conformational change of the methionine 260 residue involved in substrate recognition. (2006)
  • Author(s): Ito, K., Nakajima, Y., Onohara, Y., Takeo, M., Nakashima, K., Matsubara, F., Ito, T., Yoshimoto, T.
  • Journal Title: J Biol Chem 281(44) Pages: 33664-33676
• [Journal Article] Regulation of histone acetylation and nucleosome assembly by transcription factor JDP2. (2006)
  • Author(s): Jin, C., Kato, K., Chimura, T., Yamasaki, T., Nakade, K., Murata, T., Li, H., Pan, J., Zhao, M., Sun, K., Chiu, R., Ito, T., Nagata, K., Horikoshi, M., Yokoyama, K.K.
  • Journal Title: Nat Struct Mol Biol 13(4) Pages: 331-338
• [Journal Article] Crystallization and preliminary X-ray characterization of aminopeptidase N from Escherichia coli. (2006)
  • Author(s): Onohara, Y., Nakajima, Y., Ito, K., Xu, Y., Nakashima, K., Ito, T., Yoshimoto, T.
  • Journal Title: Acta Crystallograph Sect F Struct Biol Cryst Commun 62 Pages: 699-701
• [Journal Article] クロマチン再構築因子 (2006)
  • Author(s): 難波泰明, 梶谷卓也, 中川武弥, 伊藤 敬
  • Journal Title: 蛋白質核酸酵素 51 Pages: 2076-2082
• [Journal Article] クロマチン再構築因子 (2006)
  • Author(s): 梶谷卓也, 三笠昌樹, 伊藤 敬
  • Journal Title: 実験医学 24 Pages: 1069-1074
• [Journal Article] Regulation of histone acetylation and nucleosome assembly by transcription factor JDP2. (2006)
  • Author(s): Jin, C., K.Kato, T.Chimura, T.Yamasaki, K.Nakade, T.Murata, H.Li, J.Pan, M.Zhao, K.Sun, R Chiu, T.Ito et al.
  • Journal Title: Nature Structural & Molecular Biology. Published online : 5 March 2006
• [Journal Article] Sox9 and p300 Cooperatively Regulate Chromatin-mediated Transcription. (2005)
  • Author(s): Furumatsu, T., M. Tsuda, K. Yoshida, N. Taniguchi, T. Ito, M. Hashimoto, H. Asahara.
  • Journal Title: J Biol Chem 280 Pages: 35203-8
• [Journal Article] A histone code in meiosis: the histone kinase, NHK-1, is required for proper chromosomal architecture in Drosophila oocytes. (2005)
  • Author(s): Ivanovska, I., T. Khandan, T. Ito, T.L. Orr-Weaver.
  • Journal Title: Genes Dev 19 Pages: 2571-82
• [Journal Article] Linker histone variants control chromatin dynamics during early embryogenesis. (2005)
  • Author(s): Saeki, H., K. Ohsumi, H. Aihara, T. Ito, S. Hirose, K. Ura, Y. Kaneda.
  • Journal Title: Proc Natl Acad Sci 102 Pages: 5697-702
• [Journal Article] Crystallization and preliminary X-ray characterization of prolyl tripeptidyl aminopeptidase from Porphyromonas gingivalis. (2005)
  • Author(s): Nakajima, Y., Ito, K., Xu, Y., Yamada, N., Onohara, Y., Ito, T., Yoshimoto, T.
  • Journal Title: Acta Crystallograph Sect F Struct Biol Cryst Commun 61(Pt12) Pages: 1046-1048
• [Journal Article] The conserved kinase NHK-1 is essential for mitotic progression and unifying acentrosomal meiotic spindles in Drosophila melanogaster. (2005)
  • Author(s): Cullen, C.F., A.L.Brittle, T.Ito, H.Ohkura.
  • Journal Title: J Cell Biol 171 Pages: 593-602
• [Journal Article] Sox9 p300 Cooperatively Regulate Chromatin-mediated Transcription. (2005)
  • Author(s): Furumatsu, T., M.Tsuda, K.Yoshida, N.Taniguchi, T.Ito, M.Hashimoto, H.Asahara.
  • Journal Title: J Biol Chem 280: Pages: 35203-35208
• [Journal Article] A histone code in meiosis : the histone kinase, NHK-1, is required for proper chromosomal architecture in Drosophila oocytes. (2005)
  • Author(s): Ivanovska, I., T.Khandan, T.Ito, T.L.Orr-Weaver.
  • Journal Title: Genes Dev 19 Pages: 2571-2582
• [Journal Article] Linker histone variants control chromatin dynamics during early embryogenesis. (2005)
  • Author(s): Saeki, H., K.Ohsumi, H.Aihara, T.Ito, S.Hirose, K.Ura, Y.Kaneda.
  • Journal Title: Proc Natl Acad Sci USA 102 Pages: 5697-5702
• [Journal Article] クロマチンと病態 (2005)
  • Author(s): 中川武弥, 田頭英樹, 沖昌也, 伊藤 敬
  • Journal Title: Molecular Medicine 42 Pages: 966-972
• [Presentation] 1S11p-1ヒストン翻訳後修飾と遺伝子転写 (2009)
  • Author(s): 伊藤敬
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-21
• [Presentation] ヒストン翻訳後修飾と遺伝子転写 (2009)
  • Author(s): 伊藤敬
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2009-10-21
• [Presentation] 1S4-4 Histone modification and Transcriptional Regulation (2008)
  • Author(s): Takashi Ito
  • 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: 2008-12-09
• [Presentation] Histone modification and Transcriptional Regulation Takashi Ito, Department of Biochemistry, Nagasaki University of Medicine (2008)
  • Author(s): Takashi Ito
  • 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: 神戸ポートアイランド
  • Year and Date: 2008-12-09
• [Presentation] S1-02ヒストン蛋白修飾によるクロマチン構造変換機構 (2007)
  • Author(s): 伊藤敬
  • Organizer: 第48回日本組織細胞化学会総会、第39回日本臨床分子形態学会総会
  • Place of Presentation: 山梨
  • Year and Date: 2007-09-28
• [Presentation] 2W8-1ヒストン蛋白修飾と遺伝子転写 (2007)
  • Author(s): 伊藤敬
  • 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
• [Presentation] USP activates transcriptional initiation by isopeptide bond hydrolyzation of ubiquitylated H2A and trans-histone crosstalk (2007)
  • Author(s): Nakagawa, T., Takuya Kajitani, Shinji Togo, Norio Masuko, Yoshitaka Hishikawa, Koji Takehiko, Toshifumi Matsuyama, Hideki, Ohdan, Tsuyoshi Ikura, Masami Muramatsu and Takashi Ito
  • Organizer: Keystone Symposia
  • Place of Presentation: Colorado
• [Book] 分子生物学イラストレイテッド改訂第3版 (2008)
  • Author(s): 伊藤敬(分担執筆)
  • Publisher: 羊土社
• [Book] 転写研究集中マスター(第3章クロマチンリモデリングp.62-72) (2005)
  • Author(s): 半田宏ら編集, 伊藤敬ら分担
  • Total Pages: 172
  • Publisher: 羊土社
• [Remarks] ホームページ等
  • URL: http://www.med.nagasaki-u.ac.jp/biochem/