May 22, 2001 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 color.
"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 rate."
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 normal frequency.
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 negative effects.
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