DNA methylation-related chromatin remodeling in activity-dependent BDNF gene regulation.
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.
Martinowich
Keri
K
Neuroscience Interdepartmental Program, UCLA School of Medicine, 760 Westwood Plaza, Los Angeles, CA 90095, USA.
Hattori
Daisuke
D
Wu
Hao
H
Fouse
Shaun
S
He
Fei
F
Hu
Yan
Y
Fan
Guoping
G
Sun
Yi E
YE
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics*; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone; D018899:CpG Islands / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006655:Histone Deacetylases / Q000378:metabolism; D051783:Methyl-CpG-Binding Protein 2; D051379:Mice; D008807:Mice, Inbred BALB C; D008957:Models, Genetic; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D011189:Potassium Chloride / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000378:metabolism; D020218:Response Elements; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection
D019208:Brain-Derived Neurotrophic Factor; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2; D012097:Repressor Proteins; C099683:SIN3A transcription factor; D014157:Transcription Factors; D011189:Potassium Chloride; D006655:Histone Deacetylases; D056264:Sin3 Histone Deacetylase and Corepressor Complex