Post-translational histnoe modification and chromatin strucure

2009 Fiscal Year Final Research Report

• 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)
• Project Period (FY): 2005 – 2009
• 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

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] 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] 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
• [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] 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] 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
• [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] 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] 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
  • Year and Date: 20071211-20071215
• [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
• [Remarks] ホームページ等
  • URL: http://www.med.nagasaki-u.ac.jp/biochem/