Centers & Labs

RIKEN Center for Life Science Technologies

Epigenetics Drug Discovery Unit

Unit Leader: Takashi Umehara (Ph.D.)
Takashi  Umehara(Ph.D.)

Epigenetics is the research field that tackles information beyond genetic information, such as chemical, reversible and heritable modifications of genomic DNA and histones. We have been developing methods to reconstitute, and detect, an epigenetic nucleosome, consisting of a DNA segment and core histones, with designed chemical modifications. Through utilization of such "epi-nucleosomes" in high-throughput screening along with structure-based drug design approaches, we plan to develop molecules that regulate lineage reprogramming of a cell and/or growth of a disease-related cell for rational development of novel "epi-drugs".

Main Research Field

Medicine, dentistry, and pharmacy

Related Research Fields

Chemistry / Biology

Research Subjects

  • In vitro reconstitution of epigenetics and its application (Synthetic Biology)
  • Understanding of molecular and regulatory mechanisms of epigenetics (Structural Biology)
  • Development of regulators for epigenetic and/or genetic information (Drug Discovery)

Selected Publications

  1. Kashiwagi, K., Takahashi, M., Nishimoto, M., Hiyama, T.B., Higo, T., Umehara, T., Sakamoto, K., Ito, T. and Yokoyama, S.:
    "Crystal structure of eukaryotic translation initiation factor 2B”
    Nature. in press. 2016.
  2. Wakamori, M., Fujii, Y., Suka, N., Shirouzu, M., Sakamoto, K., Umehara, T. and Yokoyama, S.:
    "Intra- and inter-nucleosomal interactions of the histone H4 tail revealed with a human nucleosome core particle with genetically-incorporated H4 tetra-acetylation”
    Scientific Reports. 5 17204. 2015.
  3. Nagaoka, K., Hino, S., Sakamoto, A., Anan, K., Takase, R., Umehara, T., Yokoyama, S., Sasaki, Y. and Nakao, M.:
    "Lysine-specific demethylase LSD2 suppresses lipid influx and metabolism in hepatic cells"
    Mol. Cell. Biol. 35 1068–1080. 2015.
  4. Yanagisawa, T., Takahashi, M., Mukai, T., Sato, S., Wakamori, M., Shirouzu, M., Sakamoto, K., Umehara, T. and Yokoyama, S.:
    "Multiple site-specific installations of Ne-monomethyl-L-lysine into histone proteins by cell-based and cell-free protein synthesis"
    Chembiochem. 15 1830–1838. 2014.
  5. Niwa, H., Handa, N., Tomabechi, Y., Honda, K., Toyama, M., Ohsawa, N., Shirouzu, M., Kagechika, H., Hirano, T., Umehara, T. and Yokoyama, S.:
    "Crystal structures of histone methyltransferase SET7/9 in complexes with adenosylmethionine derivatives"
    Acta Cryst. D. 69 595-602. 2013.
  6. Hino, S., Sakamoto, A., Nagaoka, K., Anan, K., Wang, Y., Mimasu, S., Umehara, T., Yokoyama, S., Kosai, K.I. and Nakao, M.:
    "FAD-dependent lysine-specific demethylase-1 regulates cellular energy expenditure"
    Nature Communications. 3: 758. doi: 10.1038/ncomms1755. 2012.
  7. Ito, T., Umehara, T., Sasaki, K., Nakamura, Y., Nishino, N., Terada, T., Shirouzu, M., Padmanabhan, P., Yokoyama, S., Ito, A. and Yoshida, M.:
    "Real-time imaging of histone H4K12-specific acetylation determines the modes of action of histone deacetylase and bromodomain inhibitors"
    Chemistry & Biology. 18 495-507. 2011.
  8. Sato, S., Mimasu, S., Sato, A., Hino, N., Sakamoto, K., Umehara, T. and Yokoyama, S.:
    "Crystallographic study of a site-specifically cross-linked protein complex with a genetically incorporated photo-reactive amino acid"
    Biochemistry. 50 250-257. 2011.
  9. Mimasu, S., Umezawa, N., Sato, S., Higuchi, T., Umehara, T. and Yokoyama, S.:
    "Structurally designed trans-2-phenylcyclopropylamine derivatives potently inhibit histone demethylase LSD1/KDM1"
    Biochemistry. 49 6494-6503. 2010.
  10. Umehara, T., Nakamura, Y., Jang, M.K., Nakano, K., Tanaka, A., Ozato, K., Padmanabhan, B. and Yokoyama, S.:
    "Structural basis for acetylated histone H4 recognition by the human BRD2 bromodomain"
    J. Biol. Chem. 285 7610-7618. 2010.

Lab Members

Principal Investigator

Takashi Umehara
Unit Leader

Core Members

Satoshi Morita
Technical Scientist
Masatoshi Wakamori
Technical Scientist
Hideaki Niwa
Technical Scientist
Shin Sato
Technical Scientist
Masaki Kikuchi
Postdoctoral Researcher
Nando Das
Postdoctoral Researcher

Contact information

1-7-22-W221 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan
Tel: +81-(0)45-503-9457
Fax: +81-(0)45-503-9201

Email: takashi.umehara [at]

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