DNA methylation-related chromatin remodeling in activity-dependent BDNF gene regulation.
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.
Mesh Terms:
Animals, Brain-Derived Neurotrophic Factor, Cells, Cultured, Chromatin, Chromosomal Proteins, Non-Histone, CpG Islands, Cyclic AMP Response Element-Binding Protein, DNA Methylation, DNA-Binding Proteins, Gene Expression Regulation, Gene Silencing, Histone Deacetylases, Methyl-CpG-Binding Protein 2, Mice, Mice, Inbred BALB C, Models, Genetic, Neuronal Plasticity, Neurons, Potassium Chloride, Promoter Regions, Genetic, Repressor Proteins, Response Elements, Transcription Factors, Transcription, Genetic, Transfection
Animals, Brain-Derived Neurotrophic Factor, Cells, Cultured, Chromatin, Chromosomal Proteins, Non-Histone, CpG Islands, Cyclic AMP Response Element-Binding Protein, DNA Methylation, DNA-Binding Proteins, Gene Expression Regulation, Gene Silencing, Histone Deacetylases, Methyl-CpG-Binding Protein 2, Mice, Mice, Inbred BALB C, Models, Genetic, Neuronal Plasticity, Neurons, Potassium Chloride, Promoter Regions, Genetic, Repressor Proteins, Response Elements, Transcription Factors, Transcription, Genetic, Transfection
Science
Date: Oct. 31, 2003
PubMed ID: 14593184
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