MeCP2 and non-CG DNA methylation stabilize the expression of long genes that distinguish closely related neuron types.

ABSTRACT: The diversity of mammalian neurons is delineated by subtle gene expression differences that may require specialized mechanisms to be maintained. Neurons uniquely express the longest genes in the genome and use non-CG DNA methylation (mCA), together with the Rett syndrome protein methyl-CpG-binding protein 2 (MeCP2), to control gene expression. However, whether these distinctive gene structures and molecular machinery regulate neuronal diversity remains unexplored. Here, we use genomic and spatial transcriptomic analyses to show that MeCP2 maintains transcriptomic diversity across closely related neuron types. We uncover differential susceptibility of neuronal populations to MeCP2 loss according to global mCA levels and dissect methylation patterns driving shared and distinct MeCP2 gene reg

SUBMITTER: Moore JR 

PROVIDER: S-EPMC12369283 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature