"Our study demonstrates how early environmental factors can alter gene expression without mutating the gene itself," said Rob Waterland, Ph.D., a research fellow in the Jirtle laboratory and lead author of the study. "The implications for humans are huge because methylation is a common event in the human genome, and it is clearly a malleable effect that is subject to subtle changes in utero."
During DNA methylation, a quartet of atoms -- called a methyl group attaches to a gene at a specific point and alters its function. Methylation leaves the gene itself unchanged. Instead, the methyl group conveys a message to silence the gene or reduce its expression inside a given cell. Such an effect is referred to as "epigenetic" because it occurs over and above the gene sequence without altering any of the letters of the four-unit genetic code.
In the treated mice, one or several of the four nutrients caused the Agouti gene to become methylated, thereby reducing its expression and potentially that of other genes, as well. Moreover, the methylation occurred early during gestation, as evidenced by its widespread manifestation throughout cells in the liver, brain, kidney and tail.
"Our data suggest these changes occur early in embryonic development, before one would even be aware of the pregnancy," said Jirtle. "Any environmental condition that impacts these windows in early development can result in developmental changes that are life-long, some of them beneficial and others detrimental."
If such epigenetic alterations occur in the developing sperm or eggs, they could even be passed on to the next generation, potentially becoming a permanent change in the family line, added Jirtle. In fact, data gathered by Swedish researcher Gunnar Kaati and colleagues indicates ju
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Contact: Becky Levine
levin005@mc.duke.edu
919-684-4148
Duke University Medical Center
1-Aug-2003