Smart thanked participants and organizers for an informative and satisfying event. (Photo courtesy of John House)

Epigenome studies are expanding our understanding of how the environment influences human health and disease. To explore this leading edge of environmental health science, the NIEHS-funded Center for Human Health and the Environment (CHHE) at North Carolina State University (NCSU) held a Feb. 8 symposium titled “Epigenetics, Environment, and Human Health.” The epigenome refers to the heritable changes to DNA that affect its function without altering the genetic sequence.

“The symposium fostered an exchange that will enhance everybody’s insights and research,” said CHHE Director Rob Smart, Ph.D. “A great deal of enthusiasm came through in the talks, as well as in the poster sessions, where the room was buzzing with energy.”

Approximately 130 attendees and poster presenters from area research institutions attended, including NIEHS scientists, postdocs, and leadership.

Clarice Weinberg, Ph.D., center, acting head of the NIEHS Biostatistics and Computational Biology Branch, discussed her poster on methylation’s potential role in lessening inflammation from fine particulate air pollution. (Photo courtesy of John House)

Identical twins are not identical

Opening speaker Randy Jirtle, Ph.D., from NCSU, noted that although we are living through the era of the genome, intriguing questions remain. For example, why do individuals, especially identical twins, vary in their susceptibility to disease? “Even though their genomes are the same, their epigenomes are not,” he observed.

Jirtle and NIEHS scientist Fred Tyson, Ph.D., coined the term environmental epigenomics and co-chaired a groundbreaking symposium on the topic in 2005, when Jirtle was at Duke University.

NIEHS bioinformatician Pierre Bushel, Ph.D., spoke with Tyson, left, whose work includes directing the National Institutes of Health Roadmap Epigenomics Mapping Consortium. (Photo courtesy of John House)

Applications in biomedical research

“It’s much bigger than chemicals,” Szyf said of early life exposures that alter epigenetics. Stress and diet, including famine, also have an impact. (Photo courtesy of John House)

Two guest speakers, who study epigenetics in distinct ways, gave presentations. Moshe Szyf, Ph.D., from McGill University in Montreal, Canada, demonstrated that early life experiences influence DNA methylation, which is one form of epigenetic change. Ben Philpot, Ph.D., from the University of North Carolina at Chapel Hill (UNC), uses epigenetics to research treatment of a developmental disorder called Angelman syndrome.

Szyf, who founded the journal Epigenetics, described studies in mammals that showed that biological and physical conditions, as well as early life social environments, influence the epigenome through DNA methylation. He stressed that methylation changes are found system-wide, including in immune cells, which suggests that cellular memory may be recorded through DNA methylation.

Imprinted genes

Philpot explained that Angelman syndrome is linked to an imprinted gene, or a gene in which the copy from one parent is silenced through epigenetic change. In certain parts of the brain, he said, the paternal copy of a gene called UBE3A is normally silenced. If the maternal copy bears a mutation or is otherwise silenced, the body will lack the gene’s product, leading to Angelman syndrome. Philpot works to epigenetically awaken the silenced gene and regain its function.

In addition to differences across tissues of the body, silencing of imprinted genes can vary across the lifespan, according to David Skaar, Ph.D., from NCSU. Control of imprinted genes may also be altered by disease and exposures, he said.

NCSU scientist Mike Cowley, Ph.D., studies how cadmium exposure in early development affects the cardiovascular system. He described a mouse model system his lab developed to determine how cadmium affects gene expression.

Jirtle, left, and Cowley caught up during a break. (Photo courtesy of John House)

Insights for early career scientists

Cowley shared a cautionary tale that underscored the need for the symposium. He analyzed a few human newborn and cord blood samples with a more expensive technology, called whole genome bisulfate sequencing, which revealed DNA regions of interest that would not have been captured by a readily available approach known as a BeadChip array.

Cowley advocated for a broad approach rather than only using a single technology. “We need to be conscious of missing an enormous amount of information,” he said.

Other speakers addressed population-based mouse models, epigenome engineering, and exposures that leave epigenetic traces in the great-grandchildren of exposed individuals, which is known as transgenerational effects.

As the symposium concluded, Nicole Allard, the lab manager for NCSU researcher and symposium speaker David Aylor, Ph.D., reflected on the day. “It was remarkable to hear all the different angles, yet there was clear cohesion across the research as well.”

“It was a superb meeting,” said Tyson. “Watching how the field is evolving, it’s clear that NIEHS has been, and remains, at the fore, pushing its development.”

CHHE is one of 23 environmental health science core centers that NIEHS funds to support collaborative use of scientific resources, community outreach, and environmental health scientists’ career development.