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MeCP2 binds to 5hmc enriched within active genes and accessible chromatin in the nervous system

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TLDR
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.

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Journal ArticleDOI

The Impact of Environmental Factors on 5-Hydroxymethylcytosine in the Brain

TL;DR: Environment appears to shape 5-hmC levels in the brain, but the available literature is hampered by limitations in measurement methods, and the field of neuroepigenetics needs to adopt new tools to increase the specificity of its data and enhance biological interpretation of exposure-related changes in 5-HMC.
Journal ArticleDOI

Genome-wide characterization of cytosine-specific 5-hydroxymethylation in normal breast tissue

TL;DR: These data suggest 5hmC may participate in gene regulatory programs that are dysregulated during breast-related carcinogenesis and provide a genome-wide map of nucleotide-level 5mC in normal breast tissue.
Journal ArticleDOI

Epigenetic regulation of Fgf1 transcription by CRTC1 and memory enhancement

TL;DR: The role of histone acetylation and DNA methylation are discussed, which are two best understood epigenetic processes in memory processes, and learning-strength-dependent changes in chromatin on the fibroblast growth factor 1 gene and on the molecular events that modulate regulation of Fgf1 transcription are focused on.
Journal ArticleDOI

The Molecular Functions of MeCP2 in Rett Syndrome Pathology.

TL;DR: The full scope of MeCP2 research available in the NIH Pubmed (https://pubmed.ncbi.nlm.nih.gov/) data base to date is considered in this article.
References
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Journal ArticleDOI

Differential expression analysis for sequence count data.

Simon Anders, +1 more
- 27 Oct 2010 - 
TL;DR: A method based on the negative binomial distribution, with variance and mean linked by local regression, is proposed and an implementation, DESeq, as an R/Bioconductor package is presented.
Journal ArticleDOI

Mapping and quantifying mammalian transcriptomes by RNA-Seq.

TL;DR: Although >90% of uniquely mapped reads fell within known exons, the remaining data suggest new and revised gene models, including changed or additional promoters, exons and 3′ untranscribed regions, as well as new candidate microRNA precursors.
Journal ArticleDOI

Conversion of 5-Methylcytosine to 5-Hydroxymethylcytosine in Mammalian DNA by MLL Partner TET1

TL;DR: It is shown here that TET1, a fusion partner of the MLL gene in acute myeloid leukemia, is a 2-oxoglutarate (2OG)- and Fe(II)-dependent enzyme that catalyzes conversion of 5mC to 5-hydroxymethylcytosine (hmC) in cultured cells and in vitro.
Journal ArticleDOI

Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2.

TL;DR: This study reports the first disease-causing mutations in RTT and points to abnormal epigenetic regulation as the mechanism underlying the pathogenesis of RTT.
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