Genomic insights into MeCP2 function: A role for the maintenance of chromatin architecture

Methyl-CpG binding protein 2 (MeCP2) plays fundamental roles in the nervous system, as both gain-of-function and loss-of-function of MECP2 are associated with severe neurological conditions. Understanding the molecular function of MeCP2 will not only provide insights into the pathogenesis of MeCP2-related disorders, but will also shed light on the epigenetic regulation of neuronal function. In the past few years, a number of studies have provided mechanistic evidence that MeCP2 recruits co-repressor complexes to particular sequences of methylated DNA. Additionally, innovative design and high-throughput sequencing technologies have provided opportunities to study the effects of MeCP2 on the neuronal transcriptome at an unprecedented level of detail, demonstrating that MeCP2 modulates gene expression in a context-specific manner. These findings have raised new questions and challenged current models of MeCP2 function. In this review, we describe several recent developments, highlight future challenges, and articulate a model by which MeCP2 functions as an organizer of chromatin architecture to modulate global gene expression in the nervous system.