RIKEN Center for Life Science Technologies


  • Research

    Latest publications from CLST.
  • News

    Awards, agreements, and other news.
  • Events

    Upcoming and past events including seminars, symposiums, open days.

For Public

To let you know about our research, this area contains 4 types of information about CLST; “Article”, “Videos”, “Event” and “Study”.
At “Article”, you can read articles on interviews and lectures, and you can enjoy the videos about CLST at “Videos”. If you want to meet and talk directly with the researcher, “Visit” give you some information of such events. You can find more difficult contents to know about our research deeply at “Study”.
  • Article
  • Event
  • Videos
  • Study

Labs & Technologies

Epigenetics Drug Discovery Unit

Toward cell-fate conversion, through epigenetic regulation


* Due to the reorganization starting as new centers in April 2018, this laboratory is now belong to the Center for Biosystems Dynamics Research. As for the latest information, please see the following URL below.
> The webpage of Laboratory for Epigenetics Drug Discovery, Center for Biosystems Dynamics Research

Unit Leader
Takashi Umehara  Ph.D.

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


Research Area

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", we have been studying regulatory mechanisms of epigenetics in terms of biochemistry and structural/synthetic biology. The Epigenetics Drug Discovery Unit has 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 have been developing molecules that regulate lineage reprogramming of a cell and/or growth of a disease-related cell for rational development of novel "epi-drugs".


Reconstitution of epigenetic nucleosomes

Histone H4 protein with designed acetylation, synthesized by combination of our genetic code expansion- and cell-free protein synthesis technologies. Pinpoint introduction of acetyllysines at designed sites was confirmed by mass spectrometry. Through this technology, we are now able to reconstitute an "epi-nucleosome" as schematically shown to the right. 

Understanding of an epigenetic mechanism

Tertiary structure analysis of the BRD2 protein that is implicated in the onsets of carcinomas and atherosclerosis.

(Left) Structural mechanism how BRD2 protein recognizes one of transcriptionally-active chromatin marks (i.e. acetylation of Lys12 of histone H4).

(Right) Development of a BRD2-inhibiting compound, BIC1, based on the tertiary structure analysis. 

Regulation of epigenetics

Histone demethylase inhibitor S2101, developed by our structure-based approaches. This compound is commercially available and is utilized as one of epigenetics-regulating reagents.

Main Publications List


Crystal structure of eukaryotic translation initiation factor 2B

Kashiwagi K, Takahashi M, Nishimoto M, Hiyama TB, Higo T, Umehara T, Sakamoto K, Ito T, Yokoyama S
Nature, 351(7592), 122-125 (2016).

Lysine-specific demethylase LSD2 suppresses lipid influx and metabolism in hepatic cells.

Nagaoka K, Hino S, Sakamoto A, Anan K, Takase R, Umehara T, Yokoyama S, Sasaki Y, Nakao M.
Mol Cell Biol, 35(7), 1068-1080 (2015).

Multiple site-specific installations of Nε-monomethyl-L-lysine into histone proteins by cell-based and cell-free protein synthesis.

Yanagisawa T, Takahashi M, Mukai T, Sato S, Wakamori M, Shirouzu M, Sakamoto K, Umehara T, Yokoyama S.
ChemBioChem, 15(12), 1830-1838 (2014).

Structures of histone methyltransferase SET7/9 in complexes with adenosylmethionine derivatives.

Niwa H, Handa N, Tomabechi Y, Honda K, Toyama M, Ohsawa N, Shirouzu M, Kagechika H, Hirano T, Umehara T, Yokoyama S.
Acta Crystallogr D Biol Crystallogr, 69(Pt4), 595-602 (2013).

FAD-dependent lysine-specific demethylase-1 regulates cellular energy expenditure.

Hino S, Sakamoto A, Nagaoka K, Anan K, Wang Y, Mimasu S, Umehara T, Yokoyama S, Kosai K, Nakao M.
Nat Commun, 3, 758 (2012).

Real-time imaging of histone H4K12-specific acetylation determines the modes of action of histone deacetylase and bromodomain inhibitors.

Ito T, Umehara T, Sasaki K, Nakamura Y, Nishino N, Terada T, Shirouzu M, Padmanabhan B, Yokoyama S, Ito A, Yoshida M.
Chem Biol, 18(4), 495-507 (2011).

Crystallographic study of a site-specifically cross-linked protein complex with a genetically incorporated photoreactive amino acid.

Sato S, Mimasu S, Sato A, Hino N, Sakamoto K, Umehara T, Yokoyama S.
Biochemistry, 50(2), 250-257 (2011).

Structurally designed trans-2-phenylcyclopropylamine derivatives potently inhibit histone demethylase LSD1/KDM1.

Mimasu S, Umezawa N, Sato S, Higuchi T, Umehara T, Yokoyama S.
Biochemistry, 49(30), 6494-6503 (2010).

Structural basis for acetylated histone H4 recognition by the human BRD2 bromodomain.

Umehara T, Nakamura Y, Jang MK, Nakano K, Tanaka A, Ozato K, Padmanabhan B, Yokoyama S.
J Biol Chem, 285(10), 7610-7618 (2010).

>>>ALL Publications

Member  *concurrent


CLST was reorganized into three centers according to the RIKEN 4th Medium-Term Plan from April 1, 2018. For the latest information of Epigenetics Drug Discovery Unit, please visit the following websites.

> The webpage of Laboratory for Epigenetics Drug Discovery, Center for Biosystems Dynamics Research [http://www.bdr.riken.jp/en/research/labs/umehara-t/index.html]