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
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