University of Wisconsin researchers have developed a new method to monitor proteins responsible for deciding what genes are expressed, a development that could lead to effective treatments for cancer and other illnesses caused by genetic mutations.

Even though the human genome is the basis for what a cell can do, the human epigenome governs the expression or lack of expression of genes, biomolecular chemistry professor John Denu said.

The epigenome is an extra layer of information consisting of a complex array of chemical modifications that aid in cell differentiation by controlling which genes will be expressed in various types of cells.

Human DNA is wound around proteins known as histones, and must be read by other types of proteins in order to direct cellular function. The subtle chemical modifications on the histones guide the proteins that perform this process.

Based on the types of modifications, proteins decide which genes will be expressed and which will be silent, as well as the intensity of an expression.

With UW graduate students Adam Garske, Samuel Oliver and Emily Wagner, Denu observed the binding preferences of five or six different proteins in order to distinguish the complexity of this epigenetic code.

Through matching epigenetic information with specific interpreting proteins, they also have been able to assemble a reference library of histones with chemical modifications.

Not only do these discoveries promote the basic understanding of the molecular basis for gene expression, they also could result in the development of drugs that target protein code readers, Denu said.

“I think our ultimate goal is to understand how these epigenetic processes function normally and then be able to apply that information to systems that are not functioning normally,” Oliver said. “In other words, we want to know about epigenetic regulation because it’s interesting, but we also want to be able to fix it when it’s broken.”

Since the epigenome can dictate whether a mutated gene functions properly, disease states which are caused by one or multiple mutations, such as cancer, very often possess a strong epigenetic component, Denu said.

Denu added once a full understanding of the interaction between the proteins and the epigenetic information is realized and the code is known, treatment possibilities could be created which would counteract or correct epigenetic information that has gone awry.

“Drugs could be developed to target specifically the interaction between a protein repressing and a tumor suppressor gene and therefore could disrupt the interaction and serve as a treatment option,” Denu said.

He added even a slight alteration in diet or physical activity may influence the intensity of certain gene expressions.

The researchers will continue this work, which will become one of the main research focuses at the new Wisconsin Institute for Discovery. The Institute will also recruit more professors to aid in further discoveries in this area.

“In my opinion, one of our most exciting future endeavors involves collaborations on campus to elucidate key epigenetic proteins and complexes in stem cells and other cell types,” Oliver said.