Epigenetics and Epitranscriptomics

In its simplest terms, epigenetics is the study of the biological mechanisms — particularly those that control DNA packaging — that switch genes on and off. These mechanisms generally include tags or marks to DNA and proteins that change gene expression but not the actual sequence of DNA. By analogy, it is like a uniform and equipment for an athlete that impacts how well he or she performs but does not change who they are.

Comprehensive Cancer Center investigators are developing sophisticated technologies and chemistry methods to detect different kinds of epigenetic marks and understanding how they impact gene and cellular function. Importantly, our scientists are discovering how changes in the patterns of marks (like brand-new uniforms or equipment) are involved in cancer and may be targeted for cancer therapy.

In 2011, the laboratory of Comprehensive Cancer Center investigator Chuan He, PhD, identified the first known enzyme responsible for removing an RNA tag called N6-methyladenosine (m6A). Since then, He has identified other tag “erasers” (removes tags), discovered some tag “writers” (adds tags), and collaborated with other Comprehensive Cancer Center faculty to understand the importance of these players in cancer. The collective set of modified, or tagged, RNA is referred to as the epitranscriptome.

A study involving He’s laboratory and gynecologic oncologist Ernst Lengyel, MD, PhD, reported that 70 percent of endometrial cancers have reduced levels of m6A methylation because of mutations or reduced expression of components of the “writer” complex (Liu et al., Nat Cell Biol 20:1074-83, 2018). Because of these alterations, cancer cells are able to grow faster and form tumors more easily. By dissecting the precise molecular networks disrupted as a result, the team hopes to be able to use drugs to block or slow down tumor growth.

Additionally, in collaboration with gastroenterologist and researcher B. Marc Bissonnette, MD, He has shown that these tagged RNA molecules contribute to the development of colorectal cancer. The team received a large grant from the National Cancer Institute (NCI) to understand the molecular players involved, and further their development of a novel sensitive biomarker for colorectal cancer based on RNA tags uniquely found in tumor cells but not surrounding normal tissue.

To further these research efforts and train future experts in this field, He and Tao Pan, PhD, established the Center for Dynamic RNA Epitranscriptomes through a grant from the National Institutes of Health (NIH). This center focuses on developing technologies to decode RNA tags and is one of only eight Centers of Excellence in Genomics Science established, and the only one dedicated to RNA modifications.