Session

1-1 Epigenetic Regulation in Stem Cells

Dr. Huck-Hui Ng: Genome Institute of Singapore

Embryonic stem (ES) cells are pluripotent cells with the ability to self-renew indefinitely. These unique properties are controlled by genetic factors and chromatin structure. The exit from the self-renewing state is accompanied by changes in epigenetic chromatin modifications such as an induction in the silencing-associated histone marks. My laboratory studies the interplay between transcription factors and chromatin modifiers in maintaining the unique properties of pluripotent cells.

1-2 Research for cardiovascular development and regeneration with ES and iPS cells

Assoc. Prof. Jun K Yamashita : Laboratory of Stem Cell Differentiation, Stem Cell Research Center, Institute for Frontier Medical Sciences, Kyoto University

Recent invention of skin fibroblast-derived pluripotent cells, induced pluripotent stem (iPS) cells, opened a new gate for regenerative medicine. iPS-cell technology can provide novel approaches and strategies in both basic research and clinical field. We have been investigating cardiovascular cell differentiation and regeneration using embryonic stem (ES) cell differentiation system (Yamashita, Nature, 2000 etc). Recently, we showed a directed and systematic differentiation method of mouse iPS cells for various cardiovascular cells (Narazaki, Circulation, 2008). That would contribute to provide novel therapeutic strategies including drug discovery for cardiovascular regeneration.

2-1 Colorful Chemical Genetics

Prof. Young-tae Chang : Department of Chemistry, National University of Singapore

We are currently developing fluorescence tagged libraries for in situ target identification and a visualization of the biological events using Diversity Oriented Fluorescence Library Approach (DOFLA). The basic hypothesis is DOFLA of the same fluorescence scaffold, but with various diversity elements directly attached around the core, may selectively respond to a broader range of target proteins in intact biological system and facilitate the mechanism elucidation and target identification.

2-2 Construction of Small Molecule Biologically Active Compound Library

Prof. Isao Shimizu: Department of Applied Chemistry, School of Advanced Science and Engineering, and Institute of Chemical Biology, Waseda University

Chemical library produced through synthetic chemistry is essential for chemical biology. Organic synthesis can provide a wide variety of small molecules. We would like to present outlines of our chemical libraries based on both target-oriented synthesis and diversity-oriented synthesis. Furthermore, labeled compound libraries with fluorescent tags or stable carbon isotope are prepared. Hopefully, our chemistry opens the doors to innovation thorough collaboration with biological groups.

3-1 DNA methylation profile for regenerative medicine and drug discovery

Prof. Kunio Shiota: Department of Cellular Biochemistry, Animal Resource Sciences and Veterinary Medical Sciences, The University of Tokyo.

Epigenetic mechanism is a memory system for heritable gene functions, which enable cells to express and maintain cellular phenotypes after cell division. In mammalian genome there are substantial numbers of tissue-dependent and differentially methylated regions (T-DMRs). The DNA methylation profile consisting of T-DMRs can reflect cellular similarity and cellular status. Thus, it became possible to analyze the whole epigenomics, representing the total epigenetic marks in a given cell type. The DNA methylation profile is a powerful assessment of cells for therapeutic use and drug discovery.

3-2 IDENTIFICATION OF NOVEL EPIGENETIC REGULATORS

Dr. Ernesto Guccione: Institute of Molecular and Cell Biology (IMCB), Singapore

In recent years several groups have generated genome wide epigenetic maps of different mouse and human cell types. One of the next challenging questions in biological research is to understand how this epigenetic information is then transduced by chromatin-associated proteins to downstream effects. The projects carried out in the lab aims at identifying the network of interaction between protein-motifs that are commonly found among chromatin-associated proteins and methylhistone modifications (HMs).

3-3 Creation and maintenance of DNA methylation patterns

Prof. Shoji Tajima : Laboratory of Epigenetics, Institute for Protein Research, Osaka University

DNA methylation is one of the underlying mechanisms of epigenetic gene regulation. In mammals, DNA methylation is crucial for embryonic development and germ cell differentiation. The DNA methylation patterns are created by de novo-type DNA methyltransferases (Dnmt) Dnmt3a and Dnmt3b, and maintained by maintenance-type Dnmt1. The DNA methylation patterns marked in genome are regulated 1) by the expression timings of Dnmt, 2) with the factors recruiting Dnmt to the target methylation sites or supporting the activity, and 3) through the chromatin structure and its modifications. Since creation and maintenance of DNA methylation patterns are crucial for cell proliferation and differentiation, small chemicals that inhibit Dnmt can be good candidates for anti-carcinogenic drugs.

4-1 Chemical genetics of an anticancer agent that inhibits pre-mRNA splicing

Prof. Minoru Yoshida : Chemical Genomics Research Group, RIKEN Advanced Science Institute

Pre-mRNA translation in the cytoplasm leads to a generation of aberrant proteins that are potentially harmful. Therefore, tight control to prevent undesired pre-mRNA export is an essential requirement for gene expression. Recently, we discovered that a small molecule named spliceostatin A binds and inhibits SF3b, a subcomplex of the spliceosome, thereby allowing the leakage of pre-mRNA into the cytoplasm and subsequent translation to generate proteins containing intron-derived sequences. In particular, p27*, a C-terminally truncated form of the cell cycle inhibitor p27, is such the product of pre-mRNA and contributed to the cell cycle arrest. Spliceostatin A will serve as a useful tool for analyzing splicing, mRNA quality control, and epigenetics.

4-2 Search for Chemical "Epi" genetic Probes from Marine Invertebrates

Assoc. Prof. Yoichi Nakao: Department of Chemistry and Biochemistry, School of Advanced Science and Engineering, and Institute of Chemical Biology, Waseda University

Recently, interest has become toward finding new tools useful for studying epigenetic control of cell differentiation or dedifferentiation. Such trends may be represented by a new word of chemical "epi" genetics. In this presentation, introduction of our strategy and examples of chemical-epigenetic probes found from marine invertebrates will be presented.