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A tale of two worms: How my research is advancing the field of epigenetics

Audrey Brown explores why an important epigenetic gene is missing in some species of roundworm.

Have you ever wondered how a cell knows whether it’s supposed to be skin or muscle? Or philosophized about “nature vs. nurture,” that is, how contributions from both genetics and the environment influence physical phenotypes? Epigenetics, a relatively new field in biology, helps explain the mechanistic basis for this phenomenon—and is the field I have chosen to dedicate my doctoral studies at the University of Utah.

Audrey Brown

I sometimes find the easiest way to describe epigenetics is using a metaphor. Imagine that the DNA within a cell is an instruction manual. It contains all the instructions necessary for cellular functions — but this manual can also be modified. Epigenetic modifications (“epi” meaning “on top of”) are like “sticky-notes,” a set of additional instructions on top of the manual. These notes contain directions like “make more of this gene here” or “turn this gene off completely.” In reality, these notes take the form of chemical tags added to the DNA itself or to proteins associated with the DNA. Scientists like myself and my colleagues in Michael Werner’s lab at the School of Biological Sciences are trying to understand what type of information each of these modifications encodes, and how the set of modifications is changed by external environmental factors.

Model organisms—most commonly certain species of worm, fruit fly or fish—are useful tools for understanding the functions of epigenetic mechanisms. Just like how we learn to solve “1+1” before “192+309,” we study fundamental biological problems in simple systems, and then generalize these results to more complex organisms, including humans. I study the humble roundworms Caenorhabditis elegans and Pristionchus pacificus. In the Werner lab, we use these worms, which shared a common ancestor between 80 million and 200 million years ago, to determine how environmental factors affect simple phenotypes, connect these variations to underlying epigenetic mechanisms, and compare the epigenetic evolutionary differences between these two species.

I recently co-authored a paper in Genetics addressing this last point. For this study, we created and compared lists of all the epigenetic genes present in these two worms. For the most part they contained a similar repertoire of epigenetic genes, yet we found one striking difference: P. pacificus is missing an epigenetic protein complex called PRC2. This was a surprising result since PRC2 is one of the most conserved epigenetic protein complexes, and is essential for various cellular functions, including cell differentiation and gene repression. So how is P. pacificus able to survive without it? We found one clue with the help of Ofer Rog’s lab at the U. We were able to detect the enzymatic output of the PRC2 complex (i.e. the specific “sticky-note” it writes), which led us to conclude that a different, yet unknown enzyme has taken over the function of PRC2 in P. pacificus.

 In general, epigenetics can explain how a seemingly static set of instructions (DNA) can be influenced by environmental and other external factors. Our new study provides insight into the evolution of these mechanisms—the loss of PRC2 indicates that while the “players may have changed, the game remains the same.” In other words, the same set of conserved epigenetic modifications may be maintained by a separate set of enzymes in different organisms.

Thank you to all those who have collaborated on this project, including the Rog lab here at the University of Utah. If you are interested in learning more, you can find our new study in Genetics.

Audrey Brown is the lead author on the study, titled “Characterization of the Pristionchus pacificus ‘epigenetic toolkit’ reveals the evolutionary loss of the histone methyltransferase complex PRC2.” It appeared in the May 2024 edition the journal Genetics. Authors included Utah colleagues Michael Werner, Ofer Rog and Spencer Gordon, along with scientists from the University of Tubingen and  European Molecular Biology Laboratory in Germany and University of Exeter in the U.K. This research was supported by a grant from the National Institute of General Medical Sciences and U startup funds.