The 770th MIB Seminar
(Joint Usage/Research Center for the Multi-stratified Host Defense System)
[Seminar in English]
This seminar was supported by the collaborative research type project in collaborative research of the Medical Institute of Bioregulation.
Title
Regulations of mitotic processes by nucleosomes — molecular principles and implications in cancer biology and immunology
Speaker
Hironori Funabiki, Ph.D.
Laboratory of Chromosome and Cell Biology, The Rockefeller University
Date
Jun. 20 (Wed), 2018
17：00～18：00
Venue
Seminar Room, Main Building 1F, Medical Institute of Bioregulation
No.31 on the following linked map.
（http://www.kyushu-u.ac.jp/f/33271/2018hospital-en.pdf）
Abstract
Chromosome structure and functions dramatically change during mitosis. Although the nucleosome is a fundamental structural and functional unit of eukaryotic chromatin, its regulatory roles in mitosis are poorly understood. Through comparative chromatin proteomics analysis to identify proteins whose chromatin binding is altered in mitosis, we discovered the novel nucleosome remodeling complex CHIRRC, composed of CDCA7 and HELLS, both of which are mutated in the Immunodeficiency, Centromere instability and Facial anomalies (ICF) syndrome. We also found that the cytoplasmic DNA sensor, cGAS, a critical component of the innate immune system, gains an access to mitotic chromosomes upon nuclear envelope break down, but its DNA-induced activation is suppressed by the nucleosome. However, when cells are arrested in mitosis by taxol, cGAS slowly becomes activated and promotes apoptosis. Implications of these findings in the ICF syndrome and cancers will be discussed.
Publications
- Zierhut C., Jenness C., Kimura, H., and *Funabiki, H. (2014)
Nucleosomal regulation of chromatin composition and nuclear assembly revealed by histone depletion. Nat Struct Mol Biol, 21, 617-625. - Zierhut C. and Funabiki, H. (2017)
The cytoplasmic DNA sensor cGAS promotes mitotic cell death. bioRxiv 168070; doi: https://doi.org/10.1101/168070. - Jenness C, Giunta S, Muller MM, Kimura H, Muir TW, *Funabiki H. (2018)
HELLS and CDCA7 comprise a bipartite nucleosome remodeling complex defective in ICF syndrome. (2018) Proc Natl Acad Sci U S A. 115, E876-E885.
Contact
Motoko Unoki
Division of Epigenomics and Development, Medical Institute of Bioregulation
Tel：092(642)6761