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Switching it on or off
The makeup of a gene isn’t changed when epigenetic modifications occur. It’s the architecture that is altered by addition or subtraction of a group of molecules that activate or silence the gene. “Basically it’s just the addition of four atoms, a carbon and three hydrogens, that determine whether a gene is turned on or turned off,” says Lossie.
Methyl groups are the most common of the molecules that can act as switches to activate or silence a gene. Addition of methyl groups is called “methylation”; removal is called “demethylation.” During growth and development, the timing of a methyl group change can determine the epigenetic effect on plants and animals.
“There are certain genes that you don’t want turned on at certain stages in the life cycle,” says Scott Briggs, a Purdue biochemist who studies enzymes that affect methyl groups.
Briggs specifically looks at histone methyltransferases, a type of enzyme that has been implicated in cancers. Histones are proteins around which DNA is wrapped like thread on a spool so that an entire genome fits into cells’ nucleosomes.
Some forms of cancer develop because a methyl group shuts off a gene that normally would stop cancer. When functioning normally, one of these suppressor genes will prevent cell over-proliferation that characterizes cancers.
“If you can modulate these enzymes in cancer or other diseases, you could possibly change the outcome,” Briggs says. “That’s a nice thing about epigenetic modifications: They alter gene expression without changing the DNA sequence. Since the genetic code is maintained, we may be able to develop drugs that would alter or reverse the gene expression, or epigenetic profile, of a cancer cell.”
In a genetic mutation, DNA actually is damaged, so the gene’s sequence is disrupted, and this often is inherited. But epigenetic changes also can be inherited. So, in some cases, cancers, obesity, diabetes, behavior and even hair color could be affected in progeny and future generations, depending on when and where methyl groups or other small molecules work their magic on a gene.
Being able to reverse the effect of something your mother ate or maybe your diet is the important difference between an epigenetic change and a genetic mutation. Laboratory research already has shown that a diet change for a mother at risk for some diseases can change gene activity so that her offspring are disease free.
Passing it on
In a landmark epigenetic study, Duke University scientists fed a diet high in methyl to some obese, gold-colored mother mice that also were prone to cancer and diabetes. In these mice, methyl groups attached to a mistakenly turned-on gene in the mother and caused the obesity, odd color and disease risk. The methyl-high diet turned off the gene in the mother mice. The “fixed” gene transferred into the embryos’ chromosomes as the cells duplicated to form the offspring, which were born a normal color and size, and without the predisposition to diabetes.
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