How Epigenetics Regulate Vital Functions from Bacteria to Humans

A new review article published by BUSM researchers in Genetics & Epigenetics provides a comparative analysis of the evolution of epigenetic mechanisms from prokaryotes (bacteria) to simple (multi-cellular) and more complex eukaryotes (humans).

Epigenetics refers to mechanisms of regulating gene expression that do not involve change to the underlying DNA sequence. This is accomplished by using chemical tags which alter the function of cellular machinery responsible for gene transcription. Bacteria tag the DNA strands themselves without changing the underlying coding sequence. Eukaryote also tag DNA, but additionally tag the proteins involved in the packaging of DNA within the cell nucleus, which provides more refined levels of regulation.

According to corresponding author Sibaji Sarkar, PhD, instructor of medicine, it is intriguing to observe how new sites for tagging developed from bacteria to mammals.  “The addition of tagging proteins that are involved in folding DNA in eukaryotes provided another dimension,” he explains. These additional layers of regulation impact many important phenomena from embryogenesis and regeneration. In addition, this review includes the description of altered epigenetic changes which may lead to many types of diseases including metabolic syndrome, cardiovascular disease, autoimmune diseases, neurological disorders, aging and cancer.

For example, Sakar has previously hypothesized that the development of cancer progenitor cells may reflect an epigenetic event including silencing tumor suppressor genes, or upregulating genes that promote cell growth. “Cancer cells possibly hijack a mechanism operative in normal cells which provides a way how the methyl tagged DNA will be untagged by cutting the DNA at the site of tag and repairing it. These mechanisms possibly result in increase in copy numbers of cancer promoting genes and deletion of tumor suppressor genes. It is an interesting idea which needs to be tested.”

BUSM co-authors on the study include: Amber Willbanks, Meghan Leary, Molly Greenshields, Camila Tyminski, Karolina Lapinska, and Kathryn Haskins. Sarah Heerboth is from Vanderbilt School of Medicine.

Submitted by Jonathan Dashkoff, MD, PhD.