Homeostatic regulation of MeCP2 expression by a CREB-induced microRNA.
Both increases and decreases in methyl CpG-binding protein 2 (MeCP2) levels cause neurodevelopmental defects. We found that MeCP2 translation is regulated by microRNA 132 (miR132). Block of miR132-mediated repression increased MeCP2 and brain-derived neurotrophic factor (BDNF) levels in cultured rat neurons and the loss of MeCP2 reduced BDNF and miR132 levels in vivo. This feedback loop may provide a mechanism for homeostatic control of MeCP2 expression.
Klein
Matthew E
ME
Vollum Institute, Oregon Health & Science University, Portland, Oregon 97239, USA.
Lioy
Daniel T
DT
Ma
Lin
L
Impey
Soren
S
Mandel
Gail
G
Goodman
Richard H
RH
D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D050882:CREB-Binding Protein / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D005576:Colforsin / Q000494:pharmacology; D004347:Drug Interactions; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D051783:Methyl-CpG-Binding Protein 2 / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000494:pharmacology; D050436:Regulatory Elements, Transcriptional / Q000235:genetics; D013873:Thionucleotides / Q000494:pharmacology
D019208:Brain-Derived Neurotrophic Factor; C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; D034741:RNA, Small Interfering; D013873:Thionucleotides; D049452:Green Fluorescent Proteins; D005576:Colforsin; D050882:CREB-Binding Protein