James D. Watson and Francis Crick launched the modern era of molecular genetics when they described the structure of DNA in 1953. In the decades that followed, biologists quickly learned that DNA is transcribed into RNA and RNA into proteins, with the nucleotide bases in the DNA and RNA —A, C, G, and T — encoding the instructions for the protein.

However, in the last two decades researchers have found that information is also coded in the proteins that bind the DNA, including histone proteins, and the DNA structure itself, which together are called chromatin. Unlike the nucleotides that remain fixed unless a mutation occurs, the epigenetic information coded in the chromatin is easily reversible by cellular enzymes. Biologists now know that organisms use these reversible epigenetic modifications to change how cells behave and respond to their environment.

The Penn Epigenetics Program, directed by Shelley L. Berger, PhD, and Kenneth S. Zaret, PhD, brings together researchers from more than 50 laboratories from the Philadelphia area, including faculty from Penn Medicine, the Wistar Institute, Thomas Jefferson University, Fox Chase Cancer Center, Drexel University, and Temple University. The work extends from the molecular basis of epigenetics itself to insect behavior and novel approaches to treating human disease.


In terms of basic cell biology, researchers at Penn Medicine have found that epigenetics influence what phenotype a cell takes on, for example whether it becomes a pancreas or liver cell. Zaret's team has also found out why it has been so difficult to transform differentiated cells, such as skin cells, into embryonic-like stem cells. Researchers have also found epigenetic marks on the chromatin that help direct the process of cell division. Read more.


In the area of behavior, Penn investigators have found that epigenetic changes determine whether an ant becomes a soldier or a nurse. Whereas, in mice, epigenetic changes appear to reduce how susceptible male offspring will be to cocaine addiction if their father was exposed to the drug. Read more.


Given that the Perelman School of Medicine is focused on improving human health, perhaps it should be no surprise that the broadest swath of epigenetics research is focused on human metabolism, disease, and response to therapy, with studies looking at response to chemotherapy drugs and how high fat diets influence heart disease risk. Read more.

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