Sequence Features Accurately Predict Genome-wide MeCP2 Binding in vivo

MECP2 is critical for proper brain development and expressed at near-histone levels in neurons, but the mechanism of its genomic localization remains poorly understood. Using high-resolution MeCP2 binding data, we show that genetic features alone can predict binding with 88% accuracy. Integrating MeCP2 binding and DNA methylation in a probabilistic graphical model, we demonstrate that previously reported methylation preferences may be due to MeCP2’s affinity to GC-rich chromatin, a result replicated using published data. Furthermore, MeCP2 co-localized with nucleosomes, and Mecp2 deletion led to nucleosome repositioning. Finally, MeCP2 binding downstream of promoters correlated with increased expression in Mecp2 deficient neurons. Study of genetic and epigenetic determinants of MeCP2 binding using MeCP2 ChIP-seq, MNase-seq, Bisulfite-seq and RNA-seq. Please see individual sample record for details on experimental design.