Epigenetic Mechanisms Link Chromatin Expression to the Cell’s Metabolic State Through Key Metabolites Such as Acetyl-CoA, and this Review Examines how Cancer-Related Metabolites can Disrupt these Processes.
Epigenetic mechanisms allow cells to inherit information through DNA methylation and histone protein modifications. These changes affect chromatin structure and help proteins recognize specific modifications, with each modification requiring an enzyme that uses important metabolites. The removal of these marks also uses different metabolites, linking chromatin expression to the cell’s metabolic state. This review highlights the key roles of acetyl-CoA, S-adenosyl methionine, NAD(+), and other acyl-CoA derivatives in these processes and examines how metabolites from cancer mutations can disrupt the epigenetic program.
Metabolism and Genes
Metabolism, epigenetics, and DNA are complicated topics. However, grasping the basics can help you better understand your body and gain greater insight into disease, treatment, and how environmental factors impact your health. This simple overview will teach you what you need to know to feel informed about DNA and metabolism epigenetics, so you can take steps to improve your well-being.
First off, let’s think of DNA as an instruction manual for the body. Your DNA provides instructions to the cell on what to do and become, and how to operate. Now, if DNA is the instruction manual, then epigenetics can be compared to bookmarks, sticky tabs, and notes in the margins of that manual. Epigenetics doesn’t change the words that are written but rather calls out key pieces of information, emphasizes certain things, and leaves additional notes. They can tell the body which instructions to skip and which to follow immediately. Metabolism can be compared to the factory that makes the pens, erasers, and sticky notes. Depending on what the factory produces and in what amounts, different instructions in the DNA may be emphasized or de-emphasized, allowing the cell to prioritize certain tasks over others.
The relationship between metabolism and epigenetics is a two-way street. Changing the metabolic output changes the pattern of the epigenetic markers. And changing the epigenetic markers changes the instructions, which in turn impacts which substrates the metabolism produces. This interconnected process plays a large role in cellular energy regulation.
A high metabolic rate means the factory is producing a lot of supplies—in particular ATP, AMP, and acetyl-CoA that reflect active energy and biosynthetic pathways. The availability of these metabolites can influence which DNA instructions are emphasized by epigenetic enzymes, often supporting processes related to growth and biosynthesis when conditions are favorable. During times of low energy or metabolic stress, NAD⁺ levels can increase, activating enzymes that act like epigenetic “erasers” by removing specific histone modifications. This shifts cells away from growth‑focused programs and toward maintenance, efficiency, and stress resilience.
The way we fuel our bodies can also impact metabolism. This is called nutrient sensing. The type of supplies produced will vary based on the fuel provided—sugar vs. fat. And again, the supplies help determine how the DNA instruction manual is read.
But wait, there’s another factor in this as well. Redox balance can also impact epigenetics by influencing how genes are regulated rather than acting as a simple on-and-off switch. When the redox balance is maintained within a healthy range, cellular processes that depend on redox and epigenetic signaling tend to function properly. Genes involved in the redox metabolism are regulated in ways that support normal cellular function. However, when the Redox balance is thrown off, which can happen due to environmental stress, then the epigenetic marker placement gets disrupted. This can lead to improper signaling that is associated with cellular dysfunction and an increased risk of disease or other health problems.
So you see, DNA, metabolism, epigenetics, and redox are all closely connected. They are interdependent and are also influenced by outside factors such as diet, environment, and stress. Maintaining the proper balance is important for normal cell growth and function.
