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DNA methylation-related chromatin remodeling in activity-dependent BDNF gene regulation.

Science (New York, N.Y.) | Oct 31, 2003

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.

Pubmed ID: 14593184 RIS Download

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

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Associated grants

  • Agency: NINDS NIH HHS, Id: NS44405

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