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Epigenomically Bistable Regions across Neuron-Specific Genes Govern Neuron Eligibility to a Coding Ensemble in the Hippocampus.
- Source :
-
Cell reports [Cell Rep] 2020 Jun 23; Vol. 31 (12), pp. 107789. - Publication Year :
- 2020
-
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.<br />Competing Interests: Declaration of Interests The authors declare no competing interests.<br /> (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Alleles
Animals
DNA (Cytosine-5-)-Methyltransferases metabolism
DNA Methylation genetics
DNA Methyltransferase 3A
Dentate Gyrus metabolism
Hippocampus embryology
Male
Mice, Inbred C57BL
Mice, Knockout
Organ Specificity genetics
Epigenesis, Genetic
Hippocampus metabolism
Neurons cytology
Neurons metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 31
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 32579919
- Full Text :
- https://doi.org/10.1016/j.celrep.2020.107789