Currently, we mainly focus on the following projects:
1) How do highly conserved ATP-dependent chromatin remodeling factors regulate S phase checkpoint activity and DNA replication in the presence of DNA damage?
Understand the mechanisms by which ATP-dependent chromatin remodeling factors control cell division through regulation of the ribosome RNA gene (rDNA) locus. We have found that two highly conserved chromatin remodeling factors Isw2 and Ino80 work together to control chromatin structure at the rDNA locus. We are using biochemical, molecular genetic, and genomic approaches to elucidate the underlying mechanisms.
2) Repression of long non-coding RNA transcription by ATP-dependent chromatin remodeling factors: How do they do it, and what does it do?
Elucidating functions, regulation, and evolution of non-coding RNA (ncRNA). It was recently found that much of eukaryotic genomes are transcribed by ncRNAs. However, how many of them have biological functions, how they are regulated, and how they have evolved are largely unknown. We have systematically identified repressors of ncRNAs, and are investigating how regulation of ncRNA affects mRNA transcription. We are also investigating how ncRNA has evolved, especially upon loss of RNAi in a budding yeast lineage.
3) Regulating the timing of replication origin activation through chromatin: How does it happen, and how does it affect DNA replication?
Regulation and biological roles for higher order chromatin structure. Although there are many evidence strongly suggesting that higher order chromatin structure plays pivotal roles in controlling cell division,
cell-cycle and differentiation, little is known about actual structure, how it is regulated, how it affects
various DNA-dependent processes. Using a recently developed breakthrough genomic method Micro-C,
we are investigating higher order chromatin structure at different stages of the cell-cycle. We are also developing genetic tools to manipulate higher order chromatin structure to probe its biological roles.
4) Regulating quiescent cell state through chromatin: Who play the major roles, and at which stages? How do they do it?
Elucidating the molecular basis for quiescence. Proper control of quiescence is essential for stem cell maintenance and prevention of cancer. However, molecular mechanisms underlying entry, maintenance
and exit from quiescence remains largely unknown. It was recently found that the budding yeast S. cerevisiae can enter quiescent state that share many properties with mammalian quiescence, and a
method to purify the quiescent cell was developed. In collaboration with the Breeden lab in our Division,
we have found that a highly conserved histone deacetylase Rpd3 plays a central role in quiescence entry
by targeting more than half of all genes on yeast genome, causing global transcriptional shutoff. We are currently investigating how Rpd3-dependent global histone deacetylation affect higher order chromatin structure. We are also investigating how early stages of quiescence entry is regulated.