Emerging Insights into the Distinctive Neuronal Methylome.

The genomes of mammalian neurons are enriched for unique forms of DNA methylation, including exceptionally high levels of non-CG methylation. Here, we review recent studies defining how non-CG methylation accumulates in neurons and is read out by the critical regulator of neuronal transcription, MeCP2. We discuss the role of gene expression and genome architecture in establishing non-CG methylation and highlight emerging mechanistic insights into how non-CG methylation and MeCP2 control transcription. Further, we describe the cell type-specific functions of this methylation and explore growing evidence that disruption of this regulatory pathway contributes to neurodevelopmental disorders. These findings uncover how the distinctive epigenome in neurons facilitates the development and function of the complex mammalian brain.