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Science 302 (5646): 890-893

Copyright © 2003 by the American Association for the Advancement of Science

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}

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.

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} (Y.E.S.); gfan{at} (G.F.)

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Interaction between chromatin proteins MECP2 and ATRX is disrupted by mutations that cause inherited mental retardation.
X. Nan, J. Hou, A. Maclean, J. Nasir, M. J. Lafuente, X. Shu, S. Kriaucionis, and A. Bird (2007)
PNAS 104, 2709-2714
   Abstract »    Full Text »    PDF »
The Transcription Factor Nerve Growth Factor-Inducible Protein A Mediates Epigenetic Programming: Altering Epigenetic Marks by Immediate-Early Genes.
I. C. G. Weaver, A. C. D'Alessio, S. E. Brown, I. C. Hellstrom, S. Dymov, S. Sharma, M. Szyf, and M. J. Meaney (2007)
J. Neurosci. 27, 1756-1768
   Abstract »    Full Text »    PDF »
Partial rescue of MeCP2 deficiency by postnatal activation of MeCP2.
E. Giacometti, S. Luikenhuis, C. Beard, and R. Jaenisch (2007)
PNAS 104, 1931-1936
   Abstract »    Full Text »    PDF »
Autism-lessons from the X chromosome.
E. J. Marco and D. H. Skuse (2006)
Soc Cogn Affect Neurosci 1, 183-193
   Abstract »    Full Text »    PDF »
Enhanced anxiety and stress-induced corticosterone release are associated with increased Crh expression in a mouse model of Rett syndrome.
B. E. McGill, S. F. Bundle, M. B. Yaylaoglu, J. P. Carson, C. Thaller, and H. Y. Zoghbi (2006)
PNAS 103, 18267-18272
   Abstract »    Full Text »    PDF »

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