Epigenomically Bistable Regions across Neuron-Specific Genes Govern Neuron Eligibility to a Coding Ensemble in the Hippocampus.

Publication Type	Academic Article
Authors	Odell S, Taki F, Klein S, Chen R, Levine O, Skelly M, Nabila A, Brindley E, Gal Toth J, Dündar F, Sheridan C, Fetcho R, Alonso A, Liston C, Landau D, Pleil K, Toth M
Journal	Cell Rep
Volume	31
Issue	12
Pagination	107789
Date Published	06/23/2020
ISSN	2211-1247
Keywords	Epigenesis, Genetic, Hippocampus, Neurons
Abstract	Sensory inputs activate sparse neuronal ensembles in the dentate gyrus of the hippocampus, but how eligibility of individual neurons to recruitment is determined remains elusive. We identify thousands of largely bistable (CpG methylated or unmethylated) regions within neuronal gene bodies, established during mouse dentate gyrus development. Reducing DNA methylation and the proportion of the methylated epialleles at bistable regions compromises novel context-induced neuronal activation. Conversely, increasing methylation and the frequency of the methylated epialleles at bistable regions enhances intrinsic excitability. Single-nucleus profiling reveals enrichment of specific epialleles related to a subset of primarily exonic, bistable regions in activated neurons. Genes displaying both differential methylation and expression in activated neurons define a network of proteins regulating neuronal excitability and structural plasticity. We propose a model in which bistable regions create neuron heterogeneity and constellations of exonic methylation, which may contribute to cell-specific gene expression, excitability, and eligibility to a coding ensemble.
DOI	10.1016/j.celrep.2020.107789
PubMed ID	32579919
PubMed Central ID	PMC7440841