Epigenomically Bistable Regions across Neuron-Specific Genes Govern Neuron Eligibility to a Coding Ensemble in the Hippocampus
| Autor: | Alicia Alonso, Kristen E. Pleil, Rosa J. Chen, Caroline Sheridan, Judit Gal Toth, Robert N. Fetcho, Shannon C. Odell, Conor Liston, Elizabeth Brindley, S. Klein, Friederike Dündar, Anika Nabila, Olivia B. Levine, Faten A. Taki, Miklós Tóth, Dan A. Landau, Mary Jane Skelly |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Biology Hippocampus Article General Biochemistry Genetics and Molecular Biology DNA Methyltransferase 3A Epigenesis Genetic 03 medical and health sciences 0302 clinical medicine Gene expression medicine Animals DNA (Cytosine-5-)-Methyltransferases Epigenetics Gene Alleles Mice Knockout Neurons Dentate gyrus Methylation DNA Methylation Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure nervous system CpG site Organ Specificity Dentate Gyrus DNA methylation Neuron Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Cell reports |
| ISSN: | 2211-1247 |
| Popis: | SUMMARY 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. Graphical Abstract In Brief Odell et al. show regions within neuronal genes with bistable DNA methylation states that are associated with gene expression, excitability, and activation in the dentate gyrus of the hippocampus. These data suggest that the methylation state of bistable regions dictates, via modulating gene expression, neuron eligibility to a coding ensemble. |
| Databáze: | OpenAIRE |
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