Teaching Interests
BSC 477/L/577/L Microbial Genetics
BSC 478L Molecular Biology Lab
Research Interests
A fundamental understanding of many
processes in eukaryotic organisms, including human
diseases, requires molecular dissection of the
mechanisms through which gene expression is controlled.
The budding yeast Saccharomyces cerevisiae has proven a
valuable model with which to study a broad range of
complex cellular phenomena, including the critical
process of transcription initiation and its regulation
in response to internal or external stimuli. Of
particular interest are the multifunctional eukaryotic
DNA-binding proteins that regulate expression of
abundantly transcribed genes and act globally to
influence chromosome structure and function. One of
these factors is Rap1p, a transcriptional activator of
glycolytic and translational component genes in S.
cerevisiae. Interestingly, Rap1p function is
position-dependent; when bound at sites distinct from
those adjacent to the aforementioned genes, it can
influence telomere structure or even participate in
transcriptional silencing. The mechanism of this
functional partitioning is unknown, but seems likely to
involve interaction between Rap1p and distinct ancillary
factors specific to each of its roles in the yeast
nucleus. One such factor, Gcr1p, mediates the activation
function of Rap1p, providing an activation domain to
Rap1p/Gcr1p complexes and itself binding to a "CT box"
in DNA when the latter is adjacent to the Rap1p binding
site (UASRPG). Rap1p and Gcr1p apparently contact each
other and DNA simultaneously, forming a DNA loop. This
CT box-mediated loop is essential to UASRPG-driven
transcription near a telomere (TEL) or centromere (CEN)
but not elsewhere; we have recently discovered that it
is inert unless a third factor, Gcr2p, is present. Our
current primary goals are to:
- characterize the domains in
Gcr1p/Rap1p and Gcr1p/Gcr2p that mediate formation
of the heterotrimeric complex
- elucidate the essential role of
Gcr2p in TEL/CEN-proximal activation of
transcription
- identify the repression mechanism
that silences Rap1p/Gcr1p activation at such loci in
the absence of the CT box and Gcr2p.
In doing so, we seek to understand
these critically important aspects of gene regulation
and the molecular basis for the segregation of Rap1p's
diverse functions.
Representative Publications
Willis, K. A., K. E. Barbara, B. B.
Menon, J. Moffat, B. Andrews, and G. M. Santangelo: The
global transcriptional regulator Gcr1p mediates the
response to glucose by stimulating protein synthesis and
CLN-dependent cell cycle progression. Genetics, in
press.
Deminoff, S.J. & G.M. Santangelo.
2001. Rapip requires Gcr1p and Gcr2p homodimers to
activate ribosomal protein and glycolytic genes,
respectively. Genetics 158: 133-143.
Zeng, X. Z., Deminoff, S. J., & G. M.
Santangelo. 1997. Specialized Rap1p/Gcr1p
transcriptional activation through Gcr1p DNA contacts
requires Gcr2p, as does hyperphosphorylation of Gcr1p.
Genetics 147:493-505.
Deminoff, S., Tornow, J., & G.M.
Santangelo. 1995. Unigenic evolution: a novel genetic
method localizes a putative leucine zipper that mediates
dimerization of the Saccharomyces cerevisiae
regulator Gcr1p. Genetics 141: 1263-1274.
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