Scientists from the UNC School of Medicine and Stanford University have uncovered what may be a fundamental biological mechanism that helps organisms adapt to rapid changes to nutrients in their environments.
New findings help explain how a changing nutrient environment outside the cell could be able to communicate to the nucleus of the cell in such a way that the appropriate genes are switched on or off.
Brian Strahl is the study co-senior author and a professor and vice-chair of the Department of Biochemistry and Biophysics, Oliver Smithies Investigator at the UNC School of Medicine, and a member of the UNC Lineberger Comprehensive Cancer Center.
The study was a collaboration between Strahl’s lab and that of Ashby Morrison, Ph.D., an associate professor in the Department of Biology at Stanford University.
Morrison further elaborated that they have identified mechanisms by which cells can quickly reduce their energy consumption as soon as it becomes limited in the local environment. Expression of genes growth is extremely energy-demanding, and they need to be tightly regulated in a nutrient-limited environment to ensure survival.
The finding advances basic science by just revealing a key mechanism through which cells alter gene expression programs to adapt to the low-nutrient conditions. But it also has long-term clinical implications, including our understanding and treating of cancers.
The study identified a key yeast protein which is Taf14, that mediates crotonylation’s growth-changing functions. Proteins similar to Taf14 in humans are often disrupted in cancers, hinting that this signaling mechanism might be a future target of cancer therapy.
Fatty acids are generated as byproducts of this alternate energy production process and soon make their way to the nucleus which forces a change in gene activity that will slow the growth and otherwise adapts the cell for low-nutrient conditions.
Strahl said that It’s an elegant way that nature evolved to control the genome using metabolic events happening in the cell.
Strahl and Morrison both made these findings by studying yeast, which has a natural tendency to cycle cleanly between nutrient-rich and nutrient-poor states. This made it easy to isolate the function of histone crotonylation. The scientists now also plan to study the role of this type of epigenetic mark in humans, where it is prominent in gut and brain cells.
Strahl said that they think that this area of research could give them some key insights into how cancer cells are able to survive.