New insights into mechanisms that regulate DNA methylation patterning.

From a fertilised egg to a mature organism, cells divide and accumulate epigenetic information, which is faithfully passed on to daughter cells. DNA methylation consolidates the memory of the developmental history and, albeit very stable, it is not immutable and DNA methylation patterns can be deconstructed – a process that is essential to regain totipotency. Research into DNA methylation erasure gained momentum a few years ago with the discovery of 5-hydroxymethylcytosine, an oxidation product of 5-methylcytosine. The role of this new epigenetic modification in DNA demethylation and other potential epigenetic roles are discussed here. But what are the mechanisms that regulate deposition of epigenetic modifications? Until recently, limited direct evidence indicated that signalling molecules are able to modulate the function of epigenetic modifiers, which shape the epigenome in the nucleus of the cell. New reports in embryonic stem cell model systems disclosed a tight relationship between major signalling pathways and the DNA methylation machinery, which opens up exciting avenues in the relationship between external signals and epigenetic memory. Here, I discuss mechanisms and concepts in DNA methylation patterning, the implications in normal development and disease, and future directions.