Chemical Genetics Laboratory

Chemical Genetics is one of the new molecular genetics in which mutations in classical genetics are replaced by specific chemicals called bioprobes, and by which their unique cellular phenotypes are analyzed at the molecular level. This approach is providing more and more new insights into the molecular mechanisms underlying cellular response, cell cycle control and molecular recognition. In our laboratory, biological functions of a number of molecules targeted by bioprobes are studied by approaches using genomics, proteomics, and microbiology, in addition to chemical genetics. In particular, we focus on regulation of protein subcellular localization and protein post-translational modifications and their interplays such as acetylation, methylation ubiquitination and sumoylation. Our motto is to enjoy our research while aiming to create novel concepts in both basic and applied biologies.

Research Subjects

• Regulation of protein post-translational modifications such as acetylation
• Epigenetic regulation by splicing and histone modifications
• Identification of molecular targets for novel bioactive compounds
• Roles of DNA recombination in mitochondrial inheritance
• Secondary metabolism of pathogenic filamentous fungi and plant pest control

Publications

1. Nishimura, S., Arita, Y., Honda, M., Iwamoto, K., Matsuyama, A., Shirai, A., Kawasaki, H., Kakeya, H., Kobayashi, T., Matsunaga, S., and Yoshida, M.:
   "Marine antifungal theonellamides targets 3beta-hydroxysterol to activate Rho1 signaling" Nature Chem. Biol., 6: 519-526 (2010)
2. Schneider-Poetsch, T., Usui, T., Kaida, D., and Yoshida, M.:
   "Garbled messages and corrupted translations."
   Nature Chem. Biol., 6: 189-198 (2010)
3. Sasaki, K., Ito, T., Nishino, N., Khochbin, S., and Yoshida, M.:
   "Real-time imaging of histone H4 hyperacetylation in living cells."
   Proc. Natl. Acad. Sci. U.S.A., 106: 16257-16262 (2009)
4. Shirai, A., Matsuyama, A., Yashiroda, Y., Hashimoto, A., Kawamura, Y., Arai, R., Komatsu, Y., Horinouchi, S., and Yoshida, M.:
   "Global analysis of gel mobility of proteins and its use in target identification."
   J. Biol. Chem., 283: 10745-10752 (2008)
5. Dohi, Y., Ikura, T., Hoshikawa, Y., Katoh, Y., Ota, K., Nakanome, A., Muto, A., Omura, S., Ohta, T., Ito, A., Yoshida, M., Noda, T., and Igarashi, K.:
   "Bach1 inhibits oxidative stress-induced cellular senescence by impeding p53 function on chromatin."
   Nature Struct. Mol. Biol., 15: 1246-1254 (2008)
6. Kaida, D., Motoyoshi, H., Tashiro, E., Nojima, T., Hagiwara, M., Ishigami, K., Watanabe, H., Kitahara, T., Yoshida, T., Nakajima, H., Tani, T., Horinouchi, S., and Yoshida, M.:
   "Spliceostatin A targets SF3b and inhibits both splicing and nuclear retention of pre-mRNA"
   Nature Chem. Biol., 3: 576-583 (2007)
7. Shimazu, T., Horinouchi, S., and Yoshida, M.:
   "Multiple histone deacetylases and the CREB-binding protein regulate pre-mRNA 3'-end processing"
   J. Biol. Chem., 282: 4470-4478 (2007)
8. Matsuyama, A., Arai, R., Yashiroda, Y., Shirai, A., Kamata, A., Sekido, S., Kobayashi, Y., Hashimoto, A., Hamamoto, M., Hiraoka, Y., Horinouchi, S., and Yoshida, M.:
   "ORFeome cloning and global analysis of protein localization in the fission yeast Schizosaccharomyces pombe"
   Nature Biotechnol., 24: 841-847 (2006)
9. Yoshida, Y., Chiba, T., Tokunaga, F., Kawasaki, H., Iwai, K., Suzuki, T., Ito, Y., Matsuoka, K., Yoshida, M., Tanaka, K., and Tai, T.:
   "E3 ubiquitin ligase that recognizes sugar chains"
   Nature, 418: 438-442 (2002)
10. Matsuyama, A., Shimazu, T., Sumida, Y., Saito, A., Yoshimatsu, Y., Seigneurin-Berny, D., Osada, H., Komatsu, Y., Nishino, N., Khochbin, S., Horinouchi, S., and Yoshida, M.:
    "In vivo destabilization of dynamic microtubules by HDAC6-mediated deacetylation"
    EMBO J., 21: 6820-6831 (2002)