Major research fields
Epigenetics for Germline Development
In the development of multicellular organisms, the genome of a single fertilized oocyte generates diverse cell types with distinct gene expression profiles. Distinct gene expression profile in each cell is established by epigenetic mechanisms including DNA methylation and histone tail modifications, which are often mitotically heritable. In terminally differentiated cells, epigenetic information is relatively fixed, resulting in the loss of differentiation potential. In contrast, germline cells can reprogram their epigenetic information in order to acquire cellular totipotency and prevent the accumulation of epigenetic mutation through the generation. A Major goal of our research is to elucidate and reconstitute epigenetic mechanisms ensuring cellular totipotency. We focused on genome-wide epigenetic reprogramming in primordial germ cell (PGCs), which are the orign of both sperm and oocyte, in mice. We have previously shown that PGCs erase genome-wide methylation and H3K9me2 in their development. Now we try to elucidate and reconstitute epigenetic mechanisms in PGCs using by in vitro differentiation system of germ cells from embryonic stem cells.
Major relevant publications
- Okashita N#, Kumaki Y#, Ebi K#, Nishi M, Okamoto Y, Nakayama M, Hashimoto S, Nakamura T, Sugasawa K, Kojima N, Takada T, Okano M, Seki Y* (2014) PRDM14 promotes active DNA demethylation through the Ten-eleven translocation (TET)-mediated base excision repair pathway in embryonic stem cells. Development 141: 269-280
- Ohno R, Nakayama M, Naruse C, Okashita N, Takano O, Tachibana M, Asano M, Saitou M, Seki Y* (2013) A replication-dependent passive mechanism modulates DNA demethylation in mouse primordial germ cells. Development 140: 2892-2903
- Yamaji M#, Seki Y#, Kurimoto K#, Yabuta Y, Yuasa M, Shigeta M, Yamanaka K, Ohinata Y, Saitou M (2008) Critical function of Prdm14 for the establishment of the germ cell lineage in mice. Nat Genet 40: 1016-1022