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Andrew Feinberg, M.D.
Professor of Medicine and Director of the Center for Epigenetics at the Johns Hopkins Institute for Basic Biomedical Sciences on the Importance of Epigenetics
Epigenetics is information that is heritable during cell division other than the DNA sequence itself. If DNA is the text of the book of life, the epigenetic information provides the grammar, the structure for understanding those letters that are written down.
When you look around at different people you see that they don't look quite the same. That's largely explained by genetic differences in the DNA code. But if you were to take a person apart and look inside at their organs, look at their brain, liver, heart, muscle, you find that those different organs are extraordinarily different in how they appear and also how they function, but they all have identical DNA.
So what's different about those tissues is epigenetic information. Moreover, the differences in epigenetic information would appear to be much more profound, dramatic, than the differences in the genetic information from person to person, because these different organs look far more different from each other than one person does from the next.
Examples of epigenetic information include DNA methylation, which we understand a great deal about, and is a chemical modification of—the addition of a carbon and three hydrogen atoms to—the nucleotide cytosine in DNA, and we know how that's transmitted when cells divide.
But also people consider epigenetic information to include chromatin modification, chemical changes in the histones around which the DNA is wrapped in cells. We don't understand as much about that and how that's transmitted during cell division but we know that many of those patterns are maintained.
So the definition of epigenetics requires some sort of memory of these modifications as cells divide. It doesn't necessarily require that it be transmitted from parent to child. We're talking about memory during somatic cell division.
So the striking differences in epigenetic information are really from one tissue to another, in certain places throughout the genome. They're not everywhere. One of the major goals at the Center for Epigenetics at Hopkins has been to find where in the genome those differences really are.
Just like the Genome Project mapping the genome, people have been interested in mapping the epigenome as well and finding out where epigenetic modifications are located within the genome. Recently, our focus has been on DNA methylation. There are about 15 billion sites in the genome that theoretically could be modified in DNA methylation in a manner that would be maintained during cell division. We recently published a map of the varying DNA methylation sites across tissues and compared that to the variation of methylation sites in colon cancer and found thousands of regions that show methylation variations.
We just started to do some work on the epigenetics of stem cell biology. People have been doing stem cell research, specifically reprogramming stem cells, for several years. Most of these studies have focused on changes in gene expression, trying to identify which genes are involved in reprogramming cells. Typically people start with fibroblasts—cells that grow in skin—and try to reprogram them back into so-called pluripotent stem cells, which are capable of differentiating into most cell types in the body.
But very little work has been done to look at DNA methylation or chromatin modifications of reprogrammed cells. So we’ve started to study changes in DNA methylation during reprogramming. It’s critical to understand epigenetic changes in reprogrammed cells, whether the epigenetics look more like the original cell or a stem cell, because that could affect how the cell behaves. And knowing how a cell behaves will be important in developing stem cell therapies.
--Interviewed by Sujata Gupta