Details

Autor(en) / Beteiligte

• Odell, Shannon C.
• Taki, Faten
• Klein, Shifra Liba
• Chen, Rosa J.
• Levine, Olivia B.
• Skelly, Mary Jane
• Nabila, Anika
• Brindley, Elizabeth
• Gal Toth, Judit
• Dündar, Friederike
• Sheridan, Caroline K.
• Fetcho, Robert N.
• Alonso, Alicia
• Liston, Conor
• Landau, Dan A.
• Pleil, Kristen E.
• Toth, Miklos

Titel

Epigenomically Bistable Regions across Neuron-Specific Genes Govern Neuron Eligibility to a Coding Ensemble in the Hippocampus

Ist Teil von

• Cell reports (Cambridge), 2020-06, Vol.31 (12), p.107789-107789, Article 107789

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2020

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• 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. [Display omitted] •Numerous regions in DGCs show developmentally established methylation bistability•Increasing or reducing DNA methylation at regions alters neuron activation and excitability•Activated cells are enriched in one of the two states of bistable regions•Genes with bistable regions are associated with neuron excitability and plasticity 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.