Novel research findings over the last last five years have introduced more exceptions than rules in the field of DNA methylation in gene silencing. Whether DNA methylation stars as the cause or effect in the thickening regulatory plot continues to be discussed in labs around the world.
A British team of researchers led by Dr. Richard Meehan just shed some light on the matter in a recent study where they identified a set of genes where DNA methylation is more controlling than your –ex.
DNA methylation plays an important role in gene silencing and repressing transposable elements (TEs) in mammalian genomes. During development of primordial germ cells (PGC), DNA methylation marks are erased during extensive epigenetic reprogramming, so how does this demethylation impact gene expression and TE repression in PGCs?
The researchers showed that DNA methylation at the promoters of germline-specific genes connects genome-defense mechanisms to epigenetic reprogramming in mouse PGCs. Using a clever recovery assay after exposure to the demethylation drug, 5-azacytidine, the researchers identify a set of germline-specific genes that are dependent exclusively on promoter DNA methylation for their silencing.
In the somatic tissues where these genes are silent and methylated, their promoters possess specialized chromatin that does not have repressive histone modifications; this set appears to have a single repressive ‘lock’ to maintain silence. After losing the DNA methylation based ‘memory’ of silencing the genes stay on in somatic tissues. Why might genes be regulated in this way? It turns out that this gene set is enriched in genes involved in suppressing TE activity in germ cells, and the expression of these genes is normally activated during two phases of DNA demethylation in developing PGCs.
These findings suggest that the unique reliance on promoter DNA methylation acts as a highly tuned sensor of global DNA demethylation and enables PGCs to be primed to suppress TEs that can be potentially activated when global DNA methylation levels are reduced.
Check out the details at: Development. October, 2012