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Science 31 October 2003:
Vol. 302. no. 5646, pp. 890 - 893
DOI: 10.1126/science.1090842
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Reports

DNA Methylation-Related Chromatin Remodeling in Activity-Dependent Bdnf Gene Regulation

Keri Martinowich,1,2 Daisuke Hattori,3* Hao Wu,2* Shaun Fouse,4* Fei He,2 Yan Hu,4 Guoping Fan,1,4{dagger} Yi E. Sun1,2{dagger}

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.

1 Neuroscience Interdepartmental Program, UCLA School of Medicine, 760 Westwood Plaza, Los Angeles, CA 90095, USA.
2 Departments of Molecular and Medical Pharmacology and Psychiatry and Behavioral Sciences, UCLA School of Medicine, 760 Westwood Plaza, Los Angeles, CA 90095, USA.
3 University of California, Los Angeles (UCLA) ACCESS program, UCLA School of Medicine, 760 Westwood Plaza, Los Angeles, CA 90095, USA.
4 Department of Human Genetics, UCLA School of Medicine, 760 Westwood Plaza, Los Angeles, CA 90095, USA.

* These authors contributed equally to the work.

{dagger} To whom correspondence should be addressed. E-mail: ysun{at}mednet.ucla.edu (Y.E.S.); gfan{at}mednet.ucla.edu (G.F.)

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