Publication Date:
2003-11-01
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Martinowich, Keri -- Hattori, Daisuke -- Wu, Hao -- Fouse, Shaun -- He, Fei -- Hu, Yan -- Fan, Guoping -- Sun, Yi E -- NS44405/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2003 Oct 31;302(5646):890-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Neuroscience Interdepartmental Program, UCLA School of Medicine, 760 Westwood Plaza, Los Angeles, CA 90095, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14593184" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Brain-Derived Neurotrophic Factor/biosynthesis/*genetics
;
Cells, Cultured
;
Chromatin/*metabolism
;
*Chromosomal Proteins, Non-Histone
;
CpG Islands/*physiology
;
Cyclic AMP Response Element-Binding Protein/metabolism
;
*DNA Methylation
;
DNA-Binding Proteins/metabolism
;
*Gene Expression Regulation
;
Gene Silencing
;
Histone Deacetylases/metabolism
;
Methyl-CpG-Binding Protein 2
;
Mice
;
Mice, Inbred BALB C
;
Models, Genetic
;
Neuronal Plasticity
;
Neurons/*metabolism/physiology
;
Potassium Chloride/pharmacology
;
Promoter Regions, Genetic
;
Repressor Proteins/metabolism
;
Response Elements
;
Transcription Factors/metabolism
;
Transcription, Genetic
;
Transfection
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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