Epigenomically Bistable Regions across Neuron-Specific Genes Govern Neuron Eligibility to a Coding Ensemble in the Hippocampus.
Cell Rep
; 31(12): 107789, 2020 06 23.
Article
em En
| MEDLINE
| ID: mdl-32579919
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Epigênese Genética
/
Hipocampo
/
Neurônios
Limite:
Animals
Idioma:
En
Revista:
Cell Rep
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos