Using models of (i) histone deacetylase inhibition in HEK293T cells and (ii) Rett syndrome iPS cells carrying MECP2 mutations, our approach accurately discriminated their epigenetic states (99.6% and 96.1% accuracy, respectively) and identified the nuclear periphery as a hotspot of H3K27ac and CTCF redistribution. This evidence concerns the gene MECP2 and atypical Rett syndrome.