MECP2, a multi-talented modulator of chromatin architecture

It has been a long trip from 1992, the year of the discovery of MECP2, to the present day. What is surprising is that some of the pivotal roles of MeCP2 were already postulated at that time, such as repression of inappropriate expression from repetitive elements and the regulation of pericentric heterochromatin condensation. However, MeCP2 performs many more functions. MeCP2 is a reader of epigenetic information contained in methylated (and hydroxymethylated) DNA, moving from the 'classical' CpG doublet to the more complex view addressed by the non-CpG methylation, which is a feature of the postnatal brain. MECP2 is a transcriptional repressor, although when it forms complexes with the appropriate molecules, it can become a transcriptional activator. For all of these aspects, Rett syndrome, which is caused by MECP2 mutations, is considered a paradigmatic example of a 'chromatin disorder'. Even if the hunt for bona-fide MECP2 target genes is far from concluded today, the role of MeCP2 in the maintenance of chromatin architecture appears to be clearly established. Taking a cue from the non-scientific literature, we can firmly attest that MeCP2 is a player with 'a great future behind it'*.*V. Gassmann 'Un grande avvenire dietro le spalle'. TEA Eds.