Study Suggests G9a Enzyme May Inhibit Intestinal Inflammation

In a recent paper published in Gastroenterology, Mayo Clinic scientists found the G9a enzyme, a regulator of gene expression, may inhibit inflammatory disorders, such as inflammatory bowel disease (IBD).

Left: T cells without the drug that inhibits the enzyme G9a. Right: T cells treated with G9a inhibitors in vitro demonstrate an increase in intracellular cholesterol that will favor regulatory T cell development.

IBD is a broad term that indicates chronic inflammation of the gastrointestinal tract. An estimated 3.1 million adults in the U.S. have been diagnosed with IBD, which includes Crohn's disease and ulcerative colitis, according to the Centers for Disease Control and Prevention.

The mechanisms underlying the role of G9a in cell development are unclear, and manipulation of G9a function to treat inflammation is unexplored. Guilherme Piovezani Ramos, M.D., a gastroenterologist and Mayo Clinic Scholar in Minnesota, and William Faubion Jr., M.D., dean of Research at Mayo Clinic in Arizona, are the lead authors of the study.

William Faubion Jr., M.D., is dean of research at Mayo Clinic in Arizona

Environmental factors also have been shown to increase the risk of developing IBD. G9a is one of many epigenetic enzymes that regulate gene expression. Epigenetics is the study of the genetic changes to gene expression due to behavioral and environmental factors, and not to changes in DNA sequence. Epigenetics play a critical role in the development and progression of many diseases, including IBD.

The researchers used molecular and biochemical techniques and DNA and RNA sequencing to discover the molecular mechanism behind G9a that is driving T cell function associated with IBD. The role of G9a was then assessed using preclinical models.

Guilherme Piovezani Ramos, M.D.

The new study adds to a body of research from Dr. Faubion's lab investigating epigenetic regulators, including Enhancer of Zeste Homolog 2 (EZH2); BMI1; and Long non-coding RNAs.

The researchers say these early findings support the potential use of G9a inhibition in the treatment of gastrointestinal inflammation, including IBD and celiac disease. Their long-term goal is to characterize and modify regulatory T cells to provide effective clinical therapies for patients.

For the full author list, disclosure information and a complete list of those who funded the study, see the paper.

—Gerri Kelly