Laboratory for Mammalian Epigenetic Studies
Senior Investigator
Masaki OKANO (Ph.D.)
Cell differentiation produces a variety of cell lineages with different properties, and these properties need to be maintained in each cell lineage through mitosis during development. On the other hand, differentiated cells in certain lineages can transform to other lineages under certain conditions. These properties suggest that an epigenetic mechanism underlies stability and reversibility of cell differentiation. We will focus on one of the major epigenetic molecular mechanisms, DNA methylation, and study its function and regulatory mechanisms. How is the genomic DNA methylation pattern established? What is the function of DNA methylation at the cellular level and in the whole body? We will address these questions mainly by analyses of knockout mouse and ES cells.
- Functional analyses of DNA methyltransferase genes in development
- Functional analysis of DNA methyltransferase genes in chromosome structure
- Molecular genetic studies for Regulation of DNA methylation pattern
- March 05, 2009
- Decoding the rhythm of life
Genomic studies have now provided enough understanding to design clock genes
- Sakaue, M., Ohta, H., Kumaki, Y., Oda, M., Sakaide, Y., Matsuoka, C., Yamagiwa, A., Niwa, H., Wakayama, T., Okano, M.:
"DNA Methylation Is Dispensable for the Growth and Survival of the Extraembryonic Lineages."
Curr Biol 20, 1452-1457. (2010) . - Kumaki, Y., Oda, M., Okano, M.:
"QUMA: quantification tool for methylation analysis."
Nucleic Acids Res. 36, W170-175. doi:10.1093/nar/gkn294. (Web Server Issue). (2008). - Sharif, J., Muto, M., Takebayashi, S., Suetake, I., Iwamatsu, A., Endo, T. A., Shinga, J., Mizutani-Koseki, Y., Toyoda, T., Okamura, K., Tajima, S., Mitsuya, K., Okano, M. & Koseki, H. ( Contributed equally):
"The SRA protein Np95 mediates epigenetic inheritance by recruiting Dnmt1 to methylated DNA."
Nature 450, 908-912. (2007). - Takebayashi, S. I., Tamura, T., Matsuoka, C., Okano, M.:
"Major and essential role for DNA methylation mark in mouse embryogenesis and stable association of DNMT1 with newly replicated regions."
Mol Cell Biol 27, 8243-8258. (2007). - Kato, Y., Kaneda, M., Hata, K., Kumaki, K., Hisano, M., Kohara, Y., Okano, M., Li, E., Nozaki, M., Sasaki, H.:
"Role of the Dnmt3 family in de novo methylation of imprinted and repetitive sequences during male germ cell development in the mouse."
Hum Mol Genet 16, 2272-2280. (2007). - Oda, M., Yamagiwa, A., Yamamoto, S., Nakayama, T., Tsumura, A., Sasaki, H., Nakao, K., Li, E., and Okano, M.:
"DNA methylation regulates long-range gene silencing of an X-linked homeobox gene cluster in a lineage-specific manner"
Genes Dev 20, 3382-3394 (2006). - Tsumura, A., Hayakawa, T., Kumaki, Y., Takebayashi, S., Sakaue, M., Matsuoka, C., Shimotohno, K., Ishikawa, F., Li, E., Ueda, H. R., Nakayama, J., and Okano, M.:
"Maintenance of self-renewal ability of mouse embryonic stem cells in the absence of DNA methyltransferases Dnmt1, Dnmt3a and Dnmt3b"
Genes Cells 11, 805-814 (2006). - Ueda, Y., Okano, M., Williams, C., Chen, T., Georgopoulos, K., and Li, E.:
"Roles for Dnmt3b in mammalian development: a mouse model for the ICF syndrome"
Development 133, 1183-1192 (2006). - Dodge, J. E., Okano, M., Dick, F., Tsujimoto, N., Chen, T., Wang, S., Ueda, Y., Dyson, N., and Li, E.:
"Inactivation of Dnmt3b in mouse embryonic fibroblasts results in DNA hypomethylation, chromosomal instability, and spontaneous immortalization"
J Biol Chem 280, 17986-17991 (2005). - Kaneda, M., Okano, M., Hata, K., Sado, T., Tsujimoto, N., Li, E., and Sasaki, H.:
"Essential role for de novo DNA methyltransferase Dnmt3a in paternal and maternal imprinting"
Nature 429 (6994), 900-903 (2004).
Principal Investigator
- Masaki OKANO
- Senior Investigator
Members
- Takashi TAMURA
- Research Scientist
- Chisa MATSUOKA
- Technical Staff I