over, she realized that she was in a great position to ask important questions about whether the enzymatic activity Allis had discovered was really essential for gene regulation. “So we immediately set out to do that. We started collaborating with David Allis, and within six months or less my group had some very nice papers on the subject.” Today, the study of how the inherent DNA structure can be modified by adding acetyl groups and numerous other chemical groups that influence how genes are expressed has coalesced into one of the hottest areas of biomedical science – epigenetics. “Shelley and her colleagues have played a seminal role,” said Allis. “It started with her postdoctoral work with the genetics of these proteins. . . . And now 15 years removed, it’s really a huge enterprise of people.” In January, 2010, Time magazine brought epigenetics to the mainstream by featuring the topic as its cover story, “When Your DNA Isn’t Your Destiny.” A few years earlier, at the urging of Arthur H. Rubenstein, M.B., B.Ch., then the dean, Penn’s medical school had begun to build an epigenetics program. Looking around for someone to lead the program, Rubenstein said that he and his Penn colleagues found that “the very best person in the country was actually at The Wistar Institute, and that was Shelley Berger. She had done extremely innovative and creative work in a variety of areas of epigenetics and was already viewed as an international leader in this area.” A program was crafted with Berger as the leader, and she was recruited as director of the Penn Epigenetics Program and the Daniel S. Och University Professor in the departments of Cell & Developmental Biology and of Genetics. She was also named the 10th Penn Integrates Knowledge (PIK) University Professor, a University-wide initiative that recruits faculty whose research and teaching cross
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Shelley Berger, left, and Jessica Bryant, a graduate student in Cell & Molecular Biology.
multiple disciplines and at least two schools at Penn. Berger’s other appointment is in the Department of Biology of the School of Arts & Sciences (SAS). Shortly after her arrival at Penn, Kenneth Zaret, Ph.D., was recruited from the Fox Chase Cancer Center to serve as co-director of the Penn Epigenetics Program as well as associate director of the Penn Institute of Regenerative Medicine. Scientists on the program’s executive board come from departments ranging from Biochemistry and Biophysics to Pediatrics, and members of the program are drawn from Penn as well as The Children’s Hospital of Philadelphia, Wistar, Fox Chase, Drexel University, Thomas Jefferson University, and Temple University. According to Rubenstein, Berger and Zaret have built a program that “has become among the leading epigenetics programs in the country in a very short time.”
Beyond DNA The sequencing of the human genome was announced with much fanfare in 2003, but the Human Genome Project raised as many questions as it answered, if not more. Scientists were hoping that by mapping all the genes, they would be able to identify mutations in those genes that caused disease. But what they found was that simple disease-causing mutations, such as the mutations in the BRCA 1 or 2 genes that cause breast cancer, are relatively rare. Most diseases, even those that run in families and thus are thought to be inherited, arise through much more complicated mechanisms. What had become apparent, even before the Human Genome Project started, is that gene activity depends not just on the sequence of the gene but on whether and when that gene is expressed. And gene expression is a complicated process controlled