Crosstalk between transcriptional control and energy pathways, mediated by hub metabolites

Scientific Research on Innovative Areas, a MEXT Grant-in-Aid Project FY2011-2015

Shimizu Group: Structural analysis of the transcription environment factors that engage in crosstalk with metabolic pathways

Research Structure

Principal Investigator Toshiyuki Shimizu Toshiyuki Shimizu
Graduate School of Pharmaceutical Sciences
The University of Tokyo
Co-investigator Shoko Toma Sachiko Toma
Associate Professor
Graduate School of Pharmaceutical Sciences
The University of Tokyo
Co-investigator yuka nakajima Yuka Nakajima
Associate Professor
Life Science Center, Tsukuba Advanced Research Alliance
University of Tsukuba


We will focus on the factors involved in the generation of epigenetic information in response to energy status, as well as the factors that utilize metabolites produced in response to energy status as ligands or cofactors. These factors will be studied by a structure-based analytical approach in order to gain information about their structures at atomic resolution. In addition to x-ray crystallographic analysis, this research will employ small angle X-ray scattering method, which allows for direct structural estimation from the solution scattering curve.

Nucleomethylin (NML) epigenetically controls ribosomal protein synthesis, one of the most energy-intensive pathways in the cell. NML transmits epigenetic information, recruiting the histone methyltransferase Suv39H1 and histone deacetyltransferase SIRT1. The tumor-suppressor gene p53 is acetylated by the histone transacetylase p300, and this acetylation process is promoted by the nucleolar protein Mybbp1a. These systems both utilize hub metabolites to form the transcriptional environment. We will analyze the formation of the transcriptional environment on an atomic level in order to obtain structural knowledge about the epigenetic information factors that engage in crosstalk with metabolic processes and of their control mechanisms.

Recent Publications new

  1. Waku, T., *Nakajima, Y., Yokoyama, W., Nomura, N., Kako, K., Kobayashi, A., Shimizu, T.,and Fukamizu, A.
    NML-mediated rRNA base methylation links ribosomal subunit formation to cell proliferation in a p53-dependent manner.
    Cell Sci. 129, 2382-2393 (2016)pubmed
  2. Toma-Fukai, S., Kim, J.D., Park, K.E., Kuwabara, N., Shimizu, N., Krayukuhina, E., Uchiyama, S., Fukamizu, A., and *Shimizu, T.
    Novel helical assembly in arginine methyltransferase 8.
    J Mol Biol. J Mol Biol.  428, 1197-1208 (2016)pubmed
  3. Hasegawa, M., Toma-Fukai, S., Kim, JD., Fukamizu, A., and *Shimizu, T.
    Protein arginine methyltransferase 7 has a novel homodimer-like structure formed by tandem repeats.  
    FEBS Lett. 588, 1942-1948 (2014)pubmed
  4. Ohto, U., Usui, K., Ochi, T., Yuki, K., Satow, Y., and *Shimizu, T.
    Crystal Structure of Human β-Galactosidase: The Structural Basis of GM1 Gangliosidosis and Morquio B Diseases.
    J. Biol. Chem. 287, 1801-1812 (2012)pubmed   
  5. Usui, K., Ohto, U., Ochi, T., Shimizu, T., and Satow, Y.
    Expression, purification, crystallisation and preliminary X-ray crystallographic analysis of human β-Galactosidase.
    Acta Crystallogr. 68, 73-77 (2012)pubmed
  6. Ohto, U., Miyake, K., and *Shimizu, T.
    Crystal Structures of Mouse and Human RP105/MD-1 Complexes Reveal Unique Dimer Organization of the Toll-Like Receptor Family.
    J. Mol. Biol.
    413, 815-825 (2011)pubmed   
  7. Kokabu, Y., Murayama, Y., Kuwabara, N., Oroguchi, T., Hashimoto, H., Tsutsui, Y., Nozaki, N., Akashi, S., Unzai, S., Shimizu, T., Iwasaki, H., Sato, M., and *Ikeguchi, M.
    The fission yeast Swi5-Sfr1 complex, an activator of Rad51 recombinase, forms an extremely elongated Dogleg-shaped structure.
    J. Biol. Chem. 286, 43569-43576 (2011)pubmed   

Major Publications

  1. *Hashimoto, H., Hara, K., Hishiki, A., Kawaguchi, S., Shichijo, N., Nakamura, K., Unzai, S., Tamaru, Y., Shimizu, T., and Sato, M.
    Crystal structure and functional implication of zinc-finger domain of Nanos.
    EMBO Rep. 11, 848-853 (2010)
  2. Oda, T., Hashimoto, H., Kuwabara, N., Akashi, S., Hayashi, K., Kojima, C., Wong, HL., Kawasaki, T., Shimamoto, K., Sato, M., and *Shimizu, T.
    The structure of the N-terminal regulatory domain of a plant NADPH oxidase and its functional implications.

    J. Biol. Chem.
    285, 1435-1445 (2010)
  3. Hishiki, A., *Hashimoto, H., Hanafusa, T., Kamei, K., Ohashi, E., Shimizu, T., *Ohmori, H., and Sato, M.
    Structural basis for novel interactions between human translesion synthesis polymerases and PCNA.

    J. Biol. Chem.
    284, 10552-10560 (2009)
  4. Imasaki, T., Shimizu, T., Hashimoto, H., Hidaka, Y., Kose, S., Imamoto, N., Yamada, M., and *Sato, M.
    Structural basis for substrate recognition and dissociation by human transportin 1.

    Mol. Cell
    57-67 (2007)
  5. Arita, K., Hashimoto, H., Igari, K., Akaboshi, M., Kutsuna, S., Sato, M., and *Shimizu, T.
    Structural and Biochemical Characterization of a Cyanobacterium Circadian Clock-modifier Protein.

    J. Biol. Chem.
    282, 1128-1135 (2007)
  6. Chirifu, M., Hayashi, C., Nakamura, T., Toma, S., Shuto, T., Kai, H., Yamagata, Y., Davis, SJ., and *Ikemizu, S.
    Crystal structure of the IL-15-IL-15Ralpha complex, a cytokine-receptor unit presented in trans.

    Nat. Immunol.
    8, 1001-1007 (2007)
  7. Okuda, K., Nakamura, T., Sugita, M., Shimizu, T., and *Shikanai, T.
    A pentatricopeptide repeat protein is a site-recognition factor in chloroplast RNA editing.

    J. Biol. Chem.
    281, 37661-37667 (2006)
  8. Arita, K., Shimizu, T., Hashimoto, H., Hidaka, Y., Yamada, M., and *Sato, M.
    Structural basis for histone N-terminal recognition by human peptidylarginine deiminase 4.

    Proc. Natl. Acad. Sci. U.S.A. 103, 5291-5296 (2006)
  9. Naoe, Y., Arita, K., Hashimoto, H., Kanazawa, H., Sato, M., and *Shimizu, T.
    Structural characterization of calcineurin B homologous protein 1.
    J. Biol. Chem.
    280, 32372-32378 (2005)
  10. Arita, K., Hashimoto, H., Shimizu, T., Nakashima, K., Yamada, M., and *Sato, M.
    Structural basis for Ca2+-induced activation of human PAD4.

    Nat. Struct. Mol. Biol. 11,
    777-783 (2004)

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