MeCP2 binds to 5hmc enriched within active genes and accessible chromatin in the nervous system
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In this paper, a quantitative, genome-wide analysis of 5hmC, 5-methylcytosine (5mC), and gene expression in differentiated CNS cell types in vivo is presented.Abstract:
SUMMARY The high level of 5-hydroxymethylcytosine (5hmC) present in neuronal genomes suggests that mechanisms interpreting 5hmC in the CNS may differ from those present in embryonic stem cells. Here, we present quantitative, genome-wide analysis of 5hmC, 5-methylcytosine (5mC), and gene expression in differentiated CNS cell types in vivo. We report that 5hmC is enriched in active genes and that, surprisingly, strong depletion of 5mC is observed over these regions. The contribution of these epigenetic marks to gene expression depends critically on cell type. We identify methyl-CpG-binding protein 2 (MeCP2) as the major 5hmC-binding protein in the brain and demonstrate that MeCP2 binds 5hmC- and 5mC-containing DNA with similar high affinities. The Rett-syndrome-causing mutation R133C preferentially inhibits 5hmC binding. These findings support a model in which 5hmC and MeCP2 constitute a cell-specific epigenetic mechanism for regulation of chromatin structure and gene expression.read more
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Tet proteins influence the balance between neuroectodermal and mesodermal fate choice by inhibiting Wnt signaling
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DNA methylation in Parkinson's disease.
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Chromatin Regulation of Neuronal Maturation and Plasticity.
TL;DR: It is reviewed how chromatin regulation acts locally to modulate the expression of specific genes and more broadly to coordinate gene expression programs during transitions between cellular states to highlight the importance of epigenetic transcriptional mechanisms in postmitotic neurons.
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The chromatin basis of neurodevelopmental disorders: Rethinking dysfunction along the molecular and temporal axes.
TL;DR: A conceptual investigation of chromatin dysfunction in NDDs is undertaken with the aim of systematizing the available evidence in a new framework and teasing out the developmental vulnerabilities in human corticogenesis as a structuring entry point into the causation of N DDs.
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MeCP2 post-translational modifications: a mechanism to control its involvement in synaptic plasticity and homeostasis?
Elisa Bellini,Giulio Pavesi,Isabella Barbiero,Anna Bergo,Chetan Chandola,Mohammad Sarfaraz Nawaz,Laura Rusconi,Gilda Stefanelli,Marta Strollo,Maria Maddalena Valente,Charlotte Kilstrup-Nielsen,Nicoletta Landsberger +11 more
TL;DR: These results, together with the genome-wide distribution of MeCP2 and its capability to substitute histone H1, recall the complex regulation of histones and suggest the relevance of quickly gaining a deeper comprehension of Me CP2 PTMs, the respective writers and readers and the consequent functional outcomes.
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