Epigenetics Might Provide Clues for Mood Disorders

May 13, 2008— -- Epigenetics is among the hottest topics in medical science today. It is the subject of papers in many of the leading journals and it is a top priority for funding at the National Institutes of Health. And it could turn out to be a big part of the story in depression and bipolar disorder.

So what is epigenetics?

The term has been around since developmental biologist Conrad Waddington used it in the 1940s to refer to factors that influence how a genetic predisposition will ultimately play out in a biological or clinical outcome.

Now, in the molecular era, the term refers more narrowly to heritable information within cells that is not the DNA sequence itself.

While genetic transmission of information can be thought of as constituted by the chemical letters of the DNA sequence, epigenetic transmission can be considered to reside in the fonts of those letters, and in the punctuation.

The fonts matter. For example, take the sentences, "I hate being depressed," and "I hate being depressed." While the words are the same, the second one is a stronger statement. Or take "I hate being depressed!!!" Stronger still. Analogously, epigenetic modification of genes plays a major role in how strongly a gene is turned on.

These modifications take two forms: DNA methylation and histone marks.

DNA methylation refers to the addition of a chemical group called a methyl group to places in the DNA sequence. To use another metaphor, these act like locks on the factory door, determining whether chemical workers can come in and turn genes on.

Histones form balls of protein around which DNA wraps. They act like magnets that, when oriented plus to minus, lock the DNA into a closed position, but when oriented plus to plus, repel, and cause the DNA to open up. Various chemical modifications or marks influence the plus vs. minus state and thus help determine whether the doors to the gene are open.

Many cancer genes are known to be regulated by epigenetic machinery, including the colon cancer gene, APC, and the breast cancer gene, BRCA1.