Jang Lab Profile

Research Focus: Epigenetic regulation of chromatin dynamics in fission yeast and Role of histone methyltransferases and demethylases in tumorigenesis

We are part of the Department of Biology, Yonsei University, Seoul, Republic of Korea. Our research is focused on understanding the links between signaling, chromatin dynamics, and gene regulation in a model genetic system: the fission yeast Schizosaccharomyces pombe. We are also interested in understading the role of regulators of chromatin structures and histone modifying enzymes including histone deacetylases, histone methyltransferases, and histone demethylases. In addition, we are currently doing research project for discovery and development of anti-cancer drugs having inhibitory activities against histone-modifying enzymes.

The folding of DNA into chromatin and higher-ordered chromosome structures regulates diverse cellular processes ranging from epigenetic inheritance of gene expression patterns to chromosome dynamics. In addition to the role of heterochromatin in the maintenance of genomic integrity, heterochromatin-like structures contribute to silencing, which is an elementary gene-repression mechanism that regulates expression by packaging transcribable domains into specialized structures, or by introducing heritable modifications to chromosomal proteins.

At present, our labÂ’s primary research interest is in understanding how do the cell-signaling pathways affect the epigenetic control of higher order chromatin assembly and gene regulation, and in addition, what is the role of replication-independent (RI) nucleosome assembly and histone variants in formation of higher order chromatin structures and epigenetic memory.

Recently, we are investigating the links between signaling, chromatin dynamics, and gene regulation in the fission yeast and mammalian cell system. How do the post-translational modifications (phosphorylation, methylation, ubiquitination, sumoylation) of common silencing factors and histone variants affect and regulate heterochromatin silencing? Moreover, we have questioned how does RI assembly control assembly and disassembly of the chromatin. In addition, we have great interest on understanding the role of histone methyltransferase and demethylase family in tumorigenesis.

Our recent study revealed that two ubiquitin-conjugating enzymes, Rhp6 and UbcX, regulate heterochromatin silencing by altering the histone methylation patterns in the fission yeast S. pombe. In addition, our recent work provides evidences showing that stress-activated MAP kinase pathway might be involved in heterochromatin silencing at the mating-type locus in the fission yeast. The data might provide novel insights into roles of stress response signaling pathway in heterochromatin formation or gene silencing in higher eukaryotes.

Despite the bioligical significance of SUMO modification, the role of sumoylation in heterochromatin stability has not been understood yet. We have found a direct link between sumoylation and heterochromatin stability. Our findings showed sumoylation of the conserved heterochromatin proteins including Swi6/HP1, Chp2/HP1 and Clr4/Suv39h (H3-Lys9-methyltransferase) and by SUMO-conjygating enzyme Hus5 and direct association of Hus5/Ubc9 with heterochromatin. Thus, these data strongly suggest that sumoylation at heterochromatin plays a crucial role in stable maintenance of heterochromatin structure and function.

Moreover, we have developed a novel system including pINV1-H3-HA and pINV1-H4-HA for investigation of RI assembly in fission yeast. Here we showed that RI deposition of H3 and H4 occurs preferentially in euchromatic regions and is dependent on transcription. These data support that seleticve deposition of histone H3 at transcriptionally active chromatin by RI assembly pathway is highly conserved among diverse eukaryotic organisms ranging from fission yeast to humans.