DNA Methylation-Related Chromatin Remodeling in Activity-Dependent <i>Bdnf</i> Gene Regulation

Keri Martinowich(University of California, Los Angeles), Daisuke Hattori(University of California, Los Angeles), Hao Wu(University of California, Los Angeles), Shaun D. Fouse(University of California, Los Angeles), Fei He(University of California, Los Angeles), Yan Hu(University of California, Los Angeles), Guoping Fan(University of California, Los Angeles), Yi Eve Sun(University of California, Los Angeles)
Science
October 31, 2003
10.1126/science.1090842
Cited by 1,386

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.

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