CG or non-CG, that is the question

Cytosine methylation regulates the activity of eukaryotic genomes. Methylation is usually targeted to symmetrically CG sites, however it can also be targeted to non-CG sites either in particular tissues, like the brain in animals, or in whole organisms, as in land plants. Due to dominance of CG methylation and crosstalk between the different methylation contexts, the functional difference between CG and non-CG methylation remains elusive. By manipulating the activity of methylation machineries, we succeeded to generate a plant genome with substantial and comparable methylation levels targeted specifically to either CG sites or to symmetrically-oriented non-CG contexts. Transcriptome profiling of these engineered epigenomes discovered that non-CG methylation is a stronger transcriptional controller than CG methylation. These results imply that despite its predominance in eukaryotes, CG methylation is not necessarily the optimum context for genome regulation.