Many things in life–like diets, exercise routines, and blogs–are easier to start than maintain. The same can be said for DNA methylation. De novo methyltransferases establish DNA methylation patterns in embryonic stem cells, but exactly how somatic cells maintain these patterns is puzzling. Now researchers at the University of Southern California have identified a new self-regulating mechanism for epigenetic inheritance.
The DNA methyltransferases 3A and 3B (DNMT3A/3B) were once considered to be strictly de novo methyltransferases, but recent studies suggest that they cooperate with DNMT1 to maintain DNA methylation patterns through multiple somatic divisions. So Peter A. Jones, Gangning Liang, and co-workers examined the mechanisms by which DMT3A/3B help maintain the methylation status quo. Their studies revealed an interesting positive feedback loop for DNA maintenance methylation:
- Nucleosomes containing methylated DNA recruit and stabilize DNMT3A/3B, allowing the enzymes to stay tightly bound to the nucleosome and maintain CpG methylation in these regions
- When DNA becomes hypomethylated, DNMT3A/3B fall off the nucleosome and are degraded by the cell’s proteolytic machinery. This degradation of free enzymes helps prevent aberrant de novo methylation.
In other words, 5-mC not only recruits its catalyzing enzyme, but also regulates DNMT3A/3B protein levels. Once you start this paper, you’ll want to finish it, so check it out for yourself at PLoS Genetics, February 2011.