research

The subnuclear localization of DNA is highly regulated in all eukaryotes and has important but poorly understood effects on transcription and chromatin structure. In particular, the localization of DNA to the nuclear periphery has a clear role in establishing transcriptional repression. Recent studies in the yeast Saccharomyces cerevisiae reveal that certain genes are recruited to the nuclear periphery upon activation and that localization to the periphery promotes transcription. Genome-wide studies indicate that many transcriptionally active genes interact with components of the nuclear pore complex. This phenomenon may be conserved between yeast and metazoans.

We have extended these studies. We have discovered that gene recruitment to the nuclear periphery serves as a form of cellular memory of recent transcription, marking recently repressed genes to promote more rapid reactivation.

The focus of our current work is to understand two fundamental questions in cell biology: 1) how is the nucleus spatially organized and 2) how does this organization affect transcription? We study the dynamic recruitment of the INO1 and GAL1 genes to the nuclear periphery in Saccharomyces cerevisiae. These are the best-characterized examples of genes that undergo recruitment. Yeast offers a powerful combination of molecular genetics and biochemistry and provides an ideal model system for studying this process.

Our ultimate goal is to determine the molecular mechanisms used by cells to control the localization of genes, and to define the generality, properties and molecular mechanism of transcriptional memory.