The finding that MeCP2 represses transcriptional initiation was surprising because there is much less MeCP2 present at the beginning of genes than there is over the rest of the gene body. However, we found that there are three-dimensional DNA contacts between the gene body and the beginning of genes, suggesting that MeCP2 in gene bodies might act from a distance through these contacts to repress transcriptional initiation. Interestingly, an article that was co-published with ours found that MeCP2 represses transcription by repressing gene body enhancers, specific regions of DNA that can act from a distance to enhance transcription of genes. Ongoing studies in our lab are further exploring these new MeCP2 mechanisms to uncover the direct molecular function of MeCP2 and the genes it regulates. Our hope is that improved understanding of the direct function of MeCP2 will inspire novel therapeutic strategies for Rett syndrome.
This research couldn’t happen without RSRT and its supporters and all the families affected by Rett Syndrome that raise funds. We look forward to keeping you apprised of further progress.