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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Brain-Derived Neurotrophic Factor / biosynthesis
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Brain-Derived Neurotrophic Factor / genetics*
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Cells, Cultured
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Chromatin / metabolism*
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Chromosomal Proteins, Non-Histone*
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CpG Islands / physiology*
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Cyclic AMP Response Element-Binding Protein / metabolism
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DNA Methylation*
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DNA-Binding Proteins / metabolism
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Gene Expression Regulation*
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Gene Silencing
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Histone Deacetylases / metabolism
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Methyl-CpG-Binding Protein 2
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Mice
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Mice, Inbred BALB C
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Models, Genetic
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Neuronal Plasticity
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Neurons / metabolism*
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Neurons / physiology
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Potassium Chloride / pharmacology
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Promoter Regions, Genetic
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Repressor Proteins / metabolism
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Response Elements
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Sin3 Histone Deacetylase and Corepressor Complex
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Transcription Factors / metabolism
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Transcription, Genetic
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Transfection
Substances
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Brain-Derived Neurotrophic Factor
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Chromatin
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Chromosomal Proteins, Non-Histone
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Cyclic AMP Response Element-Binding Protein
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DNA-Binding Proteins
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Mecp2 protein, mouse
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Methyl-CpG-Binding Protein 2
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Repressor Proteins
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SIN3A transcription factor
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Transcription Factors
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Potassium Chloride
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Histone Deacetylases
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Sin3 Histone Deacetylase and Corepressor Complex