Neuronal MeCP2 is expressed at near histone-octamer levels and globally alters the chromatin state
By P. Skene, Robert S. Illingworth, Shaun Webb, Alastair R W Kerr, K. James, D. Turner, R. Andrews, A. Bird. Molecules and Cells, 2010
702 citations recorded by the source corpus.
SUMMARY MeCP2 is a nuclear protein with an affinity for methylated DNA that can recruit histone deacetylases. Deficiency or excess of MeCP2 causes severe neurological problems, suggesting that the number of molecules per cell must be precisely regulated. We quantified MeCP2 in neuronal nuclei and found that it is nearly as abundant as the histone octamer. Despite this high abundance, MeCP2 associates preferentially with methylated regions and high-throughput sequencing showed that its genome-wide binding tracks methyl-CpG density. MeCP2 deficiency results in global changes in neuronal chromatin structure, including elevated histone acetylation and a doubling of histone H1. Neither change is detectable in glia, where MeCP2 occurs at lower levels. The mutant brain also shows elevated transcription of repetitive elements. Our data argue that MeCP2 may not act as a gene-specific transcriptional repressor in neurons, but might instead dampen transcriptional noise genome-wide in a DNA methylation-dependent manner.
Subfields: Cognitive Neuroscience, Genetics, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/d73ec5922a79869874efda5c92db592f52b8a4bc
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Citations in the corpus
- Rett Syndrome and Fragile X Syndrome: Different Etiology With Common Molecular Dysfunctions (2021, background): “Several authors, to clarify the neurobiology of RTT and FXS, investigated the molecular targets of MeCP2 and of FMRP (Skene et al., 2010; Darnell et al., 2011; Baubec et al., 2013; Maxwell et al., 2013; Gabel et al., 2015; Rube et al., 2016; Maurin et al., 2018; Sawicka et al., 2019).”
- Synaptic dysfunction in neurodevelopmental disorders associated with autism and intellectual disabilities. (2012, background): “2010) and is as abundant as one molecule for every two nucleosomes (Skene et al. 2010).”
- MeCP2 binds to 5hmc enriched within active genes and accessible chromatin in the nervous system (2013, unknown): “and the fact that both 5hmC and MeCP2 are at least an order of magnitude more abundant in CNS than in the periphery (Kriaucionis and Heintz, 2009; Skene et al., 2010), we propose that binding of 5hmC by MeCP2 plays a central role in the epigenetic regulation of neural chromatin and gene expression.”