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Dr. Andrew Vershon: So, the organism that we used to study transcriptional regulation
is the yeast Saccharomyces cerevisiae. Yeast is a single cellular organism that can grow
on rich media. The yeast that we are using is actually called bakers yeast and is involved
in making bread, and it's one of the common uses of it, that making bread or making beer.
We use yeast because it serves as an excellent model system for higher eukaryotes, including
humans. Yeast is a good model system because its cheap media or inexpensive media, it has
well developed genetics. We can knock out genes, we can introduce new genes back into
it, the genome's been completely sequenced, it's relatively small, but most important
is that many of the genes in yeast are highly conserved with human genes, and so our approach
is that we try to understand how genes are regulated and how these proteins work in yeast,
and that serves as a model for understanding how the proteins in humans may work as well.
What our approach has been is that we use a combination of genetics, molecular biology,
and biochemistry to understand how these proteins work, that regulate gene expression. So, some
of the tools that we can use are so that we can go in and make mutations in a specific
gene that codes for a protein, and then see how that mutation affects the protein's activity,
so we can see whether it knocks out the protein or whether it no longer functions, or whether
it now functions better. So, we can do that in the genes that code for the proteins or
in our case, our proteins are recognizing specific sequences of DNA to turn on and off
genes, so we can mutate the sites that they bind to it as well. Transcription, or one
of the reasons we study transcription is one of the fundamental processes in biology. For
example, every cell within a human contains the same genetic information, but clearly
those cells are different functions. You know, the heart cell has different functions than
a brain cell or a liver cell. So why are there these differences? Clearly is that there are
genes that are expressed in the heart that are not expressed in the liver or the brain.
So one of the things we're trying to understand is that what regulates those expression of
genes within specific cells. Now, the way genes are expressed is that there is polymerase,
an enzyme called RNA polymerase that binds to specific DNA sites up stream with the gene,
and then they transcribe that DNA into RNA that then eventually gets translated into
protein. Now, RNA polymerase, although can carry out this process of transcription, it
requires other factors to be recruited to the promoters or to the genes itself. For
example, here, RNA polymerase won't bind to the site on its own, but if there is a factor
that binds upstream to that site that will recognize the DNA site, it will bind and it
will help recruit RNA polymerase, therefore turning this gene on. And so these activator
proteins, these proteins that recognize specific sites upstream of the gene are very important
for regulating whether a gene is off or on. So in the absence of the protein, the gene
is off, and in the presence of the protein, the gene is on. And so these are called activator
proteins, just like there are activator proteins, there's also repressor proteins, and they
work by also binding to sites and they have the opposite effect in that they prevent polymerase
from binding to the promoter and therefore turning off genes. So it's this inner play
between activators and repressors within a given cell type, though that will determine
whether a gene is on or off. What we're really interested in is understanding how do these
regulatory factors, these repressors, these activators work. How do they recognize specific
sequences and how do they prevent polymerase from working?
Announcer: For more information on Andrew Vershon and his research, please visit waksman.rutgers.edu/Waks/Vershon
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