Epigenomically Bistable Regions across Neuron-Specific Genes Govern Neuron Eligibility to a Coding Ensemble in the Hippocampus
| العنوان: | Epigenomically Bistable Regions across Neuron-Specific Genes Govern Neuron Eligibility to a Coding Ensemble in the Hippocampus |
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| المؤلفون: | 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 |
| المصدر: | Cell reports |
| بيانات النشر: | Elsevier BV, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 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 |
| الوصف: | 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. |
| تدمد: | 2211-1247 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6ee6064c96d93472e3da6453b72baac7 https://doi.org/10.1016/j.celrep.2020.107789 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....6ee6064c96d93472e3da6453b72baac7 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22111247 |
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