NSF PR 01-42 - May 16, 2001
Tom Garritano, NSF
David Gross, LSUHSC
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"Silent" DNA Speaks up for the First Time
Until now, half of all genes in certain cells were
thought to be inexpressible
By moderately raising the temperature of cells, biologists
have broken through what was considered an impermeable
barrier that kept half the genes in some cells "silent."
The surprising results, in which these heated genes
reached 500 times their normal rate of expression,
could lead to better understanding of cellular processes
involved in aging, fever and toxicity.
Biochemistry and molecular biology professor David
Gross and graduate student Edward Sekinger conducted
the research at Louisiana State University Health
Science Center (LSUHSC) with support from the National
Science Foundation's (NSF) Division of Molecular and
Cellular Biosciences. The findings appear in the current
issue of the journal Cell.
More than half the genes in a typical human cell never
get expressed due to a shield-like coating of proteins
called "chromatin." In many genes, chromatin does
not prevent the expression of DNA's genetic codes.
But in genes coated with extremely dense "heterochromatin,"
the DNA stays quarantined from triggers that would
otherwise cause transcription, the process by which
genes dictate characteristics such as hair and eye
"Until now, genes sheathed in heterochromatin were
assumed incapable of being expressed due to an absence
of trigger proteins," Gross said. "This research shows
that these proteins do naturally penetrate the heterochromatin,
but once inside cannot function. Our evidence indicates
that heating the cells activates these proteins, causing
a heat-responsive gene to be expressed at a very high
Using yeast as a model because it has many genes in
common with humans, Gross and Sekinger raised the
cells' temperature from its normal 86 degrees to 102
degrees. The cells woke up with a vengeance, expressing
the silent, heat-responsive gene at 500 times the
Messenger RNA (mRNA) is a copy of the gene's DNA that
departs from a cell nucleus to transport genetic information.
The researchers discovered that the enzyme responsible
for producing mRNA is present even on the silent genes.
The process that makes some genes silent could itself
help scientists understand aging. Yeast cells that
contain elevated concentrations of the heterochromatin
protein Sir2 show dramatically increased life-spans.
Whereas the typical yeast cell multiplies about 25
times before dying -- compared to approximately 50
times in human cells -- yeast with twice the normal
amount of Sir2 produce 30-percent more offspring.
"These findings could turn the gene-expression field
upside down," Gross said. Apart from the possible
implications for aging, the research could eventually
help explain why certain cells are more vulnerable
to fever and toxic chemicals, and how to control their