Laboratory for Developmental Genetics

Current research

The Developmental Genetics Research Group studies epigenetic regulation of organ development and stem cell functions, mediated by Polycomb group (PcG) proteins and DNA methylation (5mC) mechanisms. We showed that PcG proteins bind unmethylated CpG dinucleotides via the CxxC domain of KDM2B, which is a component of the non-canonical polycomb repressive complex 1 (ncPRC1). This promotes deposition of H3K27me3 by the polycomb repressive complex 2 (PRC2), and subsequent recruitment of the canonical PRC1 (cPRC1)- leading to transcriptional silencing. We aim to uncover the factors that regulate: (1) ncPRC1 recruitment to unmethylated CpGs, and, (2) cPRC1 recruitment downstream of PRC2. Methylated CpGs, that are not bound by PcG proteins, are substrates of DNA methylation machinery. We previously discovered that DNA methylation is faithfully maintained by the combined role of DNMT1 and NP95/UHRF1. We are now elucidating novel molecules that function upstream of NP95-DNMT1, and couple DNA replication with maintenance methylation in mammalian cells. Our group also focuses on the broad link between epigenetic factors and DNA replication. We have identified previously unknown epigenetic factors that specifically regulate replication timing in the euchromatin compartment of the genome in the S-phase. Finally, our group is responsible to operate the animal facility affiliated to Yokohama Institute that includes cryopreservation and generation of genetic resources and human iPS cell facility.