Environmental factor – October 2021: Epigenomics sheds light on environment and disease, experts say

At Society for Environmental Mutagenesis and Genomics (EMGS) From September 22 to 25, participants focused on the associations between exposure to toxic agents and the development of cancer. Although researchers understand this disease well, it is difficult to shed light on the specific biological links between a given exposure and cancer progression.

Participants also explored topics ranging from scientific tools for studying genetic mutations to the broader implications of federal cancer research funding. Several NIEHS scientists and grant recipients shared their research.

Early epigenetic changes, risk later in life

NIEHS beneficiary Cheryl Walker, Ph.D., from Baylor College of Medicine, discussed the influence of epigenetic changes on tumor development. She also discussed how a better understanding of the epigenome will advance precision environmental health, which was the focus of her recent conversation with the NIEHS and National Toxicology Program Director Rick Woychik, Ph.D.

“The genome has evolved to be maintained and to remain faithfully replicated,” Walker said. The term genome refers to the complete set of DNA of an individual.

“There are multiple mechanisms to protect and maintain genome fidelity,” she explained. “However, the epigenome is exactly the opposite. It has evolved to maintain enough plasticity to sense and respond to the environment.

While such flexibility allows the human body to adapt to stressful survival situations, it can also lead to vulnerability to adverse environmental exposures, according to Walker. Prenatal exposures, for example, can alter the epigenome in such a way as to cause individuals to overreact or insufficiently to subsequent environmental influences, including diet.

Exposure to bisphenol A

Walker shared the results of a study in which developing mice were exposed to bisphenol A (BPA) – a chemical used in the production of plastics and epoxy resins – and then fed a traditional Western diet ( rich in fat, fructose and cholesterol). The exposed mice were very prone to fatty liver disease compared to the mice which did not consume this diet after exposure to BPA.

Walker and his research group are funded by the NIEHS as part of the Exposures and responses to toxic substances by the genomic and epigenomic regulators of the Transcription II consortium, through which they explore the role of epigenetics in tumor development. Using predictive biomarkers, Walker’s team can differentiate low- and high-risk biological changes in mice as young as five months and separate the animals into risk groups.

With such research, scientists will be better able to predict whether a person is at an increased risk of developing cancer based on environmental exposures early in life, according to Walker.

Make research more relevant

In October 2019, Archer was awarded the prestigious Distinguished Investigator title from the National Institutes of Health. Learn more about honor in this article on the environmental factor. (Photo courtesy of Steve McCaw / NIEHS)

NIEHS Scientist Trevor Archer, Ph.D., tackled cancer epigenetics by focusing on the role of chromatin in the epigenetic regulation of gene expression in response to exposure to hormones . He heads the institute’s epigenetics and stem cell biology laboratory, which studies chromatin remodeling complexes, epigenetics, and embryonic stem cell pluripotency.

More work is needed to make sure the results are relevant to everyone, according to Archer.

“Most of the large genomic and epigenomic datasets are really not representative of the entire human population,” he said, noting that many tissues are dimorphic or slightly different depending on the biological sex of one person.

“We have to make sure that the basic data is representative,” Archer added. “It is an exciting and rich period for epigenetics. There are more tools available, and our ability to do genomic studies gives us a real opportunity to bring some semblance of organization to this information.

The nine sons of the dragon

Biophysical chemist Xiaoliang Xie, Ph.D., from Peking University, opened his presentation with a Chinese proverb.

“The dragon has nine sons, and each is different,” he said, referring to the fact that no two cells are the same in the human body. Therefore, genomic variations need to be studied at the single cell level because cellular changes are not synchronized, according to Xie.

His research group is at the forefront of studying cell mutations using multiplexed amplification of end marking of complementary strands, a method that reduces the costs of genome sequencing. According to Xie, this approach could benefit thousands of Chinese families with monogenic diseases, which are diseases linked to a single gene.

Sharpless shared an overview of age-related causes of cancer at an event in October 2020 hosted by the NIEHS, NCI and the National Institute on Aging. (Photo courtesy of NCI)

Director of the National Cancer Institute (NCI) Ned Sharpless, MD, shared studies at his institute and stressed that adopting new methods of genomic analysis will shed light on when environmental exposure may be linked to cancer.

Sharpless noted that NCI’s alignment with the Biden administration’s cancer research priorities will help ensure scientific advancements in the future, and he discussed a recent collaboration with the NIEHS.

“The NCI has decided to have a meeting with internal and external scientists – with the NIEHS – in May,” he said. “We heard some very interesting presentations on the state of the art in this area, and topics included mutational signatures, exposome monitoring, animal studies, modeling, etc. We will publish the summaries of the meetings soon. “

Quotes:
Wang T, Pehrsson EC, Purshotham D, Li D, Zhuo X, Zhang B, Lawson HA, Province MA, Krapp C, Lan Y, Coarfa C, Katz TA, Tang WY, Wang Z, Biswal S, Rajagopalan S, Colacino JA , Tsai ZT, Sartor MA, Neier K, Dolinoy DC, Pinto J, Hamanaka RB, Mutlu GM, Patisaul HB, Aylor DL, Crawford GE, Wiltshire T, Chadwick LH, Duncan CG, Garton AE, McAllister KA; Consortium CIBLE II, Bartolomei MS, Walker CL, Tyson FL. 2018. The NIEHS Target II consortium and environmental epigenomics. Nat Biotechnol 36 (3): 225-227.

Xing D, Tan L, Chang CH, Li H, Xie XS. 2021. Accurate detection of SNV in single cells by whole genome amplification based on complementary strand transposon. Proc Natl Acad Sci USA 118 (8): e2013106118.

(Kelley Christensen is a writer and contract writer for the NIEHS Office of Communications and Public Liaison.)