Acute Exercise Remodels Promoter Methylation in Human Skeletal Muscle
- Transient promoter methylation occurs after an acute exercise
- Ex vivo muscle contraction mimics exercise-induced hypomethylation
- Caffeine mediates DNA hypomethylation in myocytes, implicating a role for Ca2+ release
DNA methylation is a covalent biochemical modification controlling chromatin structure and gene expression. Exercise elicits gene expression changes that trigger structural and metabolic adaptations in skeletal muscle. We determined whether DNA methylation plays a role in exercise-induced gene expression. Whole genome methylation was decreased in skeletal muscle biopsies obtained from healthy sedentary men and women after acute exercise. Exercise induced a dose-dependent expression of PGC-1α, PDK4, and PPAR-δ, together with a marked hypomethylation on each respective promoter. Similarly, promoter methylation of PGC-1α, PDK4, and PPAR-δ was markedly decreased in mouse soleus muscles 45 min after ex vivo contraction. In L6 myotubes, caffeine exposure induced gene hypomethylation in parallel with an increase in the respective mRNA content. Collectively, our results provide evidence that acute gene activation is associated with a dynamic change in DNA methylation in skeletal muscle and suggest that DNA hypomethylation is an early event in contraction-induced gene activation.
Exercise is an environmental factor that affects gene-expression, i.e., which genes are made active. Exercise itself has immediate impacts on your DNA. The wierd thing about this study though is that caffeine also has similar impacts. Again it is an environmental factor that affects gene expression.
The New Scientist explains it this way:
Now there is no excuse to avoid the gym: just one hour of exercise instantly changes your genes to boost the breakdown of fat.
Juleen Zierath and Romain Barrès at the Karolinska Institute in Stockholm, Sweden, and colleagues looked for epigenetic changes – the addition of a methyl group to genes – in muscle cells during strenuous exercise. To do so, the team collected biopsies from the thigh muscles of eight men who led relatively sedentary lives, both before and after an hour of exercise.
Several genes involved in fat metabolism that were methylated before the exercise lost their methyl group. Such demethylation allows genes to more easily make proteins, which suggests that more proteins involved in the breakdown of fat are being made after exercise, says Zierath.
The group was surprised to see these effects happen so quickly. They think calcium, produced in muscle cells during exercise, may be involved since subjecting the same biopsies to caffeine – which also increases calcium in muscles – caused the same demethylation.
Unfortunately, you would get caffeine intoxication before gaining the same effects from coffee as an hour-long workout, says Zierath.
Here is how Science Daily explained the story:
The new study shows that the DNA within skeletal muscle taken from people after a burst of exercise bears fewer chemical marks (specifically methyl groups) than it did before exercise. Those changes take place in stretches of DNA that are involved in turning "on" genes important for muscles' adaptation to exercise.
When the researchers made muscles contract in lab dishes, they saw a similar loss of DNA methyl groups. Exposure of isolated muscle to caffeine had the same effect.
Zierath explained that caffeine does mimic the muscle contraction that comes with exercise in other ways, too. She doesn't necessarily recommend anyone drink a cup of joe in place of exercise. It's nevertheless tempting to think that athletes who enjoy a coffee with their workout might just be on to something.
Broadly speaking, the findings offer more evidence that our genomes are much more dynamic than they are often given credit for. Epigenetic modifications that turn genes on and back off again can be incredibly flexible events. They allow the DNA in our cells to adjust as the environment shifts.