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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.

Pubmed ID: 14593184

Authors

  • Martinowich K
  • Hattori D
  • Wu H
  • Fouse S
  • He F
  • Hu Y
  • Fan G
  • Sun YE

Journal

Science (New York, N.Y.)

Publication Data

October 31, 2003

Associated Grants

  • Agency: NINDS NIH HHS, Id: NS44405

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