MeCP2 binds to 5hmc enriched within active genes and accessible chromatin in the nervous system
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.read more
Citations
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Rett syndrome from bench to bedside: recent advances
TL;DR: The latest advances on the molecular function of Mecp2 and the new animal and cellular models developed to better study Rett syndrome are reported and the latest innovative therapeutic approaches are presented.
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Vitamin C regulates Schwann cell myelination by promoting DNA demethylation of pro-myelinating genes
Tyler C. Huff,David W. Sant,Vladimir Camarena,Derek J. Van Booven,Nadja S. Andrade,Sushmita Mustafi,Paula V. Monje,Gaofeng Wang +7 more
TL;DR: It is found that maternal dietary vitamin C deficiency causes peripheral nerve hypomyelination throughout early development in resulting offspring and that vitamin C up‐regulates 10 pro‐myelinating genes which exhibit elevated 5hmC content in both the promoter and gene body regions of these loci following treatment.
Journal ArticleDOI
Cytosine modifications in the honey bee (Apis mellifera) worker genome
TL;DR: What may distinguish honey bees from other model animals, how the epigenome can influence worker behavioral task separation, and how future studies can answer central questions about the role of the epigenomes in social behavior are discussed.
Journal ArticleDOI
Chromatin Environment and Cellular Context Specify Compensatory Activity of Paralogous MEF2 Transcription Factors
Shahriyar P. Majidi,Naveen C. Reddy,Michael J. Moore,Hao Chen,Tomoko Yamada,Milena M. Andzelm,Timothy J. Cherry,Linda Hu,Michael E. Greenberg,Azad Bonni +9 more
TL;DR: In this paper, a single and double conditional knockout of myocyte enhancer factor 2 (MEF2) family TFs in granule neurons of the mouse cerebellum was used to uncover genome-wide functional interdependency between paralogous transcription factors in the brain.
Journal ArticleDOI
Methyl-CpG Binding Protein 2 (Mecp2) Regulates Sensory Function Through Sema5b and Robo2
Wan Y. Leong,Zhi Han Lim,Vladimir Korzh,Vladimir Korzh,Thomas Pietri,Eyleen L. K. Goh,Eyleen L. K. Goh +6 more
TL;DR: The sensory deficits caused by Mecp2 deficiency mirror the diminished sensory response observed in Rett syndrome patients and suggests that zebrafish could be an unconventional but useful model for this disorder manifesting defects that are not easily studied in full using rodent models.
References
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Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2.
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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.