Rett syndrome (RTT) is a devastating neurodevelopmental disease resulted in basically by loss-of-characteristic mutations in methyl-CpG-binding protein 2 (MECP2) (1). MeCP2 is a DNA binding protein (2) that controls gene expression, nonetheless the explicit molecular mechanism one day of which MeCP2 loss drives RTT pathology stays unclear, partly due to the a decided DNA motif that specifies MeCP2-DNA interactions is lacking. On net page 1411 of this topic, Ibrahim et al. (3) cloak that MeCP2 binds modified cytosine in cytosine-adenine (CA) dinucleotide repeats, offering a modern signature DNA motif for MeCP2 binding. MeCP2 protects CA repeats from high nucleosome occupancy, raising questions about the outcome of this binding on affirming chromatin structure in neurons.