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

Research paper by Keri K Martinowich, Daisuke D Hattori, Hao H Wu, Shaun S Fouse, Fei F He, Yan Y Hu, Guoping G Fan, Yi E YE Sun

Indexed on: 01 Nov '03Published on: 01 Nov '03Published in: Science



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.