Scientists are making important progress toward documenting how pollutants in the environment affect the epigenome, which refers to chemical signals that attach to DNA and modify its function without changing the DNA itself. Grantees in the second phase of the Toxicant Exposures and Responses by Genomic and Epigenomic Regulators of Transcription (TaRGET) Program, known as the TaRGET II consortium, met to discuss next steps at a May 2-4 meeting at NIEHS.
“We know the environment affects our health, and many scientists consider the epigenome to be a crucial point of impact,” said Fred Tyson, Ph.D., who is leading TaRGET II as part of the NIEHS Environmental Epigenetics Program, along with colleagues Lisa Chadwick, Ph.D., and Kimberly McAllister, Ph.D. “This will be the first scientific effort to systematically record how known harmful environmental exposures, like metals, particulate air pollution, and endocrine disrupting chemicals modify epigenomic signatures in mice.”
The project is a follow-on to the National Institutes of Health Roadmap Epigenomics Project, which documented over 120 epigenomes from human tissues, cells, and embryonic stem cells.
“The epigenome is a collection of chemical signals on DNA and the proteins that DNA is wrapped around. These signals are part of a larger process that directs how genes are turned on and off in different types of cells,” said Chadwick. “We are learning more and more about the role that the epigenome plays in normal development, as well as disease.”
Comparing epigenetic changes across tissues
According to Tyson, each type of cell in the body has a unique epigenome, although the underlying DNA sequence is identical. TaRGET II will compare epigenetic changes from exposure to the same environmental pollutant in several types of mouse tissues at the same time. Researchers hope to determine whether epigenetic changes in easily obtained biological samples, such as blood, can simulate changes in tissues, such as the brain, that are difficult, if not impossible, to sample in humans.
Paul Wade, Ph.D., senior scientist at NIEHS who conducts related research, said this is a critical question to answer. “With people, we simply cannot sample most tissues of interest for a particular disease or exposure,” he explained. “Blood, on the other hand, is usually readily available, and TaRGET II directly addresses how well blood may serve as a surrogate.”
Cheryl Walker, Ph.D., from the Texas A&M Health Science Center, and Marisa Bartolomei, Ph.D., from the University of Pennsylvania, presented the range of tissues grantees will study, including liver, uterus, brain, placenta, and blood.
A publicly available resource
Tyson explained that one of the project goals is to store the findings in resources that will be available for use by other scientists. “Making data publicly accessible is one of the primary reasons for the consortium,” he said. “The data coordinating center, led by Ting Wang, Ph.D., at Washington University in St. Louis, is going to develop a sustainable database, so the data will be accessible after the project funding ends.”
Wade agreed that the study will provide an important scientific foundation. “TaRGET II will set a baseline for other studies to expand on epigenetic impacts of exposure and the relationship to disease,” he said.
(Virginia Guidry, Ph.D., is a technical writer and public information specialist in the NIEHS Office of Communications and Public Liaison and a regular contributor to the Environmental Factor.)