Scientists from UNC-Chapel Hill have created a new way to investigate epigenetic mechanisms important in diseases ranging from Alzheimer’s to cancers.
University of North Carolina scientists have created a new research tool, based on the fruit fly, to help crack the histone code. This research tool can be used to better understand the function of histone proteins, which play critical roles in the regulation of gene expression in animals and plants.
This work, published in the journal Developmental Cell, opens the door to experiments that are expected to uncover new biology important for a host of conditions, such as neurological diseases, diabetes, obesity, and especially cancer, which has become a hotbed of epigenetic research.
“People think cancer is a disease of uncontrolled proliferation, but that’s just one aspect of it,” said Robert Duronio, PhD, professor of biology and genetics and co-senior author. “Cancer is actually a disease of development in which the cells don’t maintain their proper functions; they don’t do what they’re supposed to be doing.” Somehow, the gene regulation responsible for proper cell development goes awry.
One aspect of gene regulation involves enzymes placing chemical tags or modifications on histone proteins – which control a cell’s access to the DNA sequences that make up a gene. Properly regulated access allows cells to develop, function, and proliferate normally. The chemical modification of histones is thought to be a form of epigenetic information – information separate from our DNA – that controls gene regulation. This idea is based on the study of the enzymes that chemically modify histones. However, there is a flaw in this argument.
“In complex organisms, such as fruit flies, mice, and humans, scientists have only been able to infer how these enzymes mechanistically accomplish their tasks,” said Daniel McKay, PhD, assistant professor of genetics and biology and first author of the paper. “It’s been technically impossible to directly study the role of histone modifications. Now, through our collaboration between UNC biologists, we’ve been able to develop a tool in fruit flies to directly test the function of histones independently of the enzymes that modify them.”
This is crucial because therapies, such as cancer drugs, can target histones. With this new research tool, scientists will be able to better study thousands of enzyme-histone interactions important for human health.
“If you think of the genome as a recipe book, then you could say we’ve made it possible to know that there are hidden ingredients that help explain how specific recipes turn out correctly or not,” said Greg Matera, PhD, professor of biology and genetics and co-senior author of the paper. “That’s the first step in scientific discovery – knowing that there are things we need to look for and then searching for them.”
Brian Strahl, PhD, professor of biochemistry and Biophysics in the School of Medicine, is also a principal investigator of this study. Duronio, Matera, and McKay are professors in the UNC School of Medicine and the College of Arts and Sciences.
Strahl, Duronio, and Matera are members of the UNC Lineberger Comprehensive Cancer center. Matera, Duronio, and McKay are members of the Integrative Program for Biological and Genome Sciences. Duronio is the director of the program.
National Institutes of Health and the University of North Carolina funded this research.