<Research interests>

   It has been shown that non-coding RNAs regulate gene expression at the level of post-transcription in both eukaryotes and prokaryotes. For instance, miRNAs and siRNAs are incorporated into a multi-protein complex termed miRNP/RISC, which in turn degrades cognate mRNAs or represses translation. Previous studies have demonstrated that non-coding RNAs also play an important role in heterochromatin assembly and DNA methylation. Using the fission yeast Schizosaccharomyces pombe as a model system, we have shown that 1) RNAi machinery in S. pombe is required for Clr4/Suv39h-mediated histone H3 Lys9 methylation, which creates a binding site for chromodomain proteins including Swi6/HP1; 2) RITS, an RNAi effector complex, links siRNA production and heterochromatin assembly; 3) siRNAs in RITS are derived from common repetitive sequences embedded within heterochromatic domains; 4) RNAi factors such as the fission yeast Argonaute Ago1 and RNA-dependent RNA polymerase Rdp1 stably associate with heterochromatin to process transcripts from heterochromatin in cis; and 5) RNA polymerase activity of Rdp1 is essential for RNAi. These findings have contributed to the understanding of RNAi-directed epigenetic control of chromatin.

   Histone deacetylation as well as RNAi-mediated histone methylation is necessary to assemble heterochromatin. We focused a fission yeast histone deacetylase (HDAC) Clr3 to investigate how HDACs participate in the formation of the silent chromatin. We found that 1) Clr3 mainly deacetylates histone H3 Lys14 acetylation, which is associated with active transcription, 2) Clr3 is a component of SHREC, which contains a DNA-binding protein and a SNF2-type chromatin remodeler, 3) SHREC limits RNA polymerase II occupancy at heterochromatin through its enzymatic activities, histone deacetylase and SNF2 ATPase. These results demonstrates that both histone deacetylation and nucleosome positioning are required for heterochromatic silencing.

   Our group is currently trying to understand the mechanisms by which eukaryotic cells maintain genomic stability.

<Recent publications>

1. Sugiyama T., Cam H.P,. Sugiyama R., Noma K., Zofall M., Kobayashi R., and Grewal S.I. SHREC, histone deacetylase- and SNF2 ATPase-containing complex, mediates heterochromatic transcriptional silencing. Cell, 128: 491-504. 2007, Erratum in Cell,129: 1227.

2. Yamada T., Fischle W., Sugiyama T., Allis C.D., and Grewal S.I. The nucleation and maintenance of heterochromatin by a histone deacetylase in fission yeast. Mol. Cell., 20: 173-185. 2005

3. Cam H.P., Sugiyama T., Chen E.S., Chen X., FitzGerald P.C., and Grewal S.I. Comprehensive analysis of heterochromatin- and RNAi-mediated epigenetic control of the fission yeast genome.

Nat. Genet., 37: 809-819. 2005

4. Sugiyama T., Cam H., Verdel A., Moazed D., and Grewal S.I. RNA-dependent RNA polymerase is an essential component of a self-enforcing loop coupling heterochromatin assembly to siRNA production.

Proc. Natl. Acad. Sci. USA., 102: 152-157. 2005

5. Noma K., Sugiyama T., Cam H., Verdel A., Zofall M., Jia S., Moazed D., and Grewal S.I. RITS acts in cis to promote RNA interference-mediated transcriptional and post-transcriptional silencing.

Nat. Genet., 36: 1174-1180. 2004

6. Verdel A., Jia S., Gerber S., Sugiyama T., Gygi S., Grewal S.I., and Moazed D. RNAi-mediated targeting of heterochromatin by the RITS complex. Science, 303: 672-676. 2004

<Contact info.>

Tomoyasu Sugiyama, PhD

Laboratory of Advanced Research D-225

1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577 JAPAN

TEL. +81-29-853-8049

FAX. +81-29-853-5983

Last update: Sep. 8th, 2008