Non-CG DNA methylation and MeCP2 stabilize repeated tuning of long genes that distinguish closely related neuron types.

ABSTRACT: The extraordinary diversity of neuron types in the mammalian brain is delineated at the highest resolution by subtle gene expression differences that may require specialized molecular mechanisms to be maintained. Neurons uniquely express the longest genes in the genome and utilize neuron-enriched non-CG DNA methylation (mCA) together with the Rett syndrome protein, MeCP2, to control gene expression, but the function of these unique gene structures and machinery in regulating finely resolved neuron type-specific gene programs has not been explored. Here, we employ epigenomic and spatial transcriptomic analyses to discover a major role for mCA and MeCP2 in maintaining neuron type-specific gene programs at the finest scale of cellular resolution. We uncover differential susceptibility to MeCP

SUBMITTER: Moore JR 

PROVIDER: S-EPMC10862856 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature