Wednesday, October 25, 2006

Epigenetics and Methylation

Science News (June 24, subscriber-only) had a nice feature article on Epigenetics and methylation's role. I thought their explanation of how the epigenetic marks attach to DNA was particularly clear. I've read about methylation before, but never come across a description of the mechanism.

As early as the 1940s, researchers who couldn't explain some of an organism's attributes by straightforward Mendelian genetics started calling these aberrant traits epigenetic, says Randy Jirty, a researcher who studies gene control at Duke University in Durham, N.C. "'Epigenetics' literally means 'above the genome,'" he explains.

Scientists eventually learned how apt the name was. Inspecting the double helix turned up hundreds of thousands of what scientists colloquially call "marks"—places where DNA is tagged with carbon and hydrogen bundles known as methyl groups. Enzymes attach methyl groups only at points on the genome where two DNA components—cytosine and guanine—meet. These components often cluster near the beginning of a gene, where proteins attach to turn on genes. If a methyl group blocks a protein from binding, the gene typically stays switched off.

In recent years, scientists have learned that methylation isn't the only mark that changes whether genes are expressed. Various chemical groups clip on to histones, the spools around which DNA wraps when it condenses into chromosomes. These groups can affect how tightly DNA is packed. Although histone modification is not as well studied as methylation, researchers have shown that genes on loosely packed DNA are more likely to be expressed than are those on DNA that's tightly wound.

Most of these epigenetic marks are set by cells long before an animal's birth, says Jirtle. Each type of cell, from liver to skin to muscle, carries a distinct pattern of methylation and histone modification that, for the long term, switch genes on or off in the pattern necessary for the cell to do its job.

However, Jirtle adds, not all of these marks are set in stone. Outside factors during development can change which DNA segments are epigenetically modified, setting the stage for traits that linger into adulthood.

Jirtle's group did some studies with mice whose coat color can be changed epigenetically according to whether their diet is enriched or impoverished with methylation-inducing supplements. The supplements also affect disease susceptibility. They can prove that methylation mediates the signals because they can trace the presence of the methyl groups in subjects that receive different treatments, and they can change the signals by administering drugs that add or remove methyl groups selectively.

The interesting consequence of epigenetics via methylation is that parents and uterine environment have some control of the epigenetic markers of offspring separate from the DNA's message. Recent work is showing that the epigenetic markers can also be changed throughout an organism's lifespan, changing susceptibility to diseases and predisposing other somatic effects. None of this is surprising; I'm describing it merely to provide background for anyone who wouldn't otherwise understand the context. The benefit here is the clear explanation of how the methyl decoration works. Wikipedia has a more in-depth explanation and provides more discussion of consequences. I still like Science News' simple clarity.

No comments: