Proceedings of the National Academy of Sciences · 2007 · 376 citations · 40 references
Life SciencesGeneticsMolecular GeneticsEpigenomicsGene ExpressionMolecular NeuroscienceChromatinEpigenetic Regulation In NeuronsGenomic ImprintingMolecular NeurogeneticsPromoter ArchitecturePromoter RegulationCpg Island MethylationCpg Island Methylation PatternsDifferentially Methylated RegionsGenomic Imprinting MechanismsMecp2 FunctionNeuronal Dna MethylationPromoter Cpg IslandsPromoter Cpg Methylation
Mutations in MECP2 cause the autism-spectrum disorder Rett syndrome. MeCP2 is predicted to bind to methylated promoters and silence transcription. However, the first large-scale mapping of neuronal MeCP2-binding sites on 26.3 Mb of imprinted and nonimprinted loci revealed that 59% of MeCP2-binding sites are outside of genes and that only 6% are in CpG islands. Integrated genome-wide promoter analysis of MeCP2 binding, CpG methylation, and gene expression revealed that 63% of MeCP2-bound promoters are actively expressed and that only 6% are highly methylated. These results indicate that the primary function of MeCP2 is not the silencing of methylated promoters.
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Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription
Peter Lloyd Jones, Gert Jan C. Veenstra, Paul A. Wade et al. · Nature Genetics · 1998 · 2.7K citations