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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.
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