PMID:14593184

Citation	Martinowich, K, Hattori, D, Wu, H, Fouse, S, He, F, Hu, Y, Fan, G and Sun, YE (2003) DNA methylation-related chromatin remodeling in activity-dependent BDNF gene regulation. Science 302:890-3
Abstract	In conjunction with histone modifications, DNA methylation plays critical roles in gene silencing through chromatin remodeling. Changes in DNA methylation perturb neuronal function, and mutations in a methyl-CpG-binding protein, MeCP2, are associated with Rett syndrome. We report that increased synthesis of brain-derived neurotrophic factor (BDNF) in neurons after depolarization correlates with a decrease in CpG methylation within the regulatory region of the Bdnf gene. Moreover, increased Bdnf transcription involves dissociation of the MeCP2-histone deacetylase-mSin3A repression complex from its promoter. Our findings suggest that DNA methylation-related chromatin remodeling is important for activity-dependent gene regulation that may be critical for neural plasticity.
Links	PubMed Online version:10.1126/science.1090842
Keywords	Animals; Brain-Derived Neurotrophic Factor/biosynthesis; Brain-Derived Neurotrophic Factor/genetics; Cells, Cultured; Chromatin/metabolism; Chromosomal Proteins, Non-Histone; CpG Islands/physiology; Cyclic AMP Response Element-Binding Protein/metabolism; DNA Methylation; DNA-Binding Proteins/metabolism; Gene Expression Regulation; Gene Silencing; Histone Deacetylases/metabolism; Methyl-CpG-Binding Protein 2; Mice; Mice, Inbred BALB C; Models, Genetic; Neuronal Plasticity; Neurons/metabolism; Neurons/physiology; Potassium Chloride/pharmacology; Promoter Regions, Genetic; Repressor Proteins/metabolism; Response Elements; Transcription Factors/metabolism; Transcription, Genetic; Transfection
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