Homeostatic regulation of MeCP2 expression by a CREB-induced microRNA

Nat Neurosci. 2007 Dec;10(12):1513-4. doi: 10.1038/nn2010. Epub 2007 Nov 11.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Brain-Derived Neurotrophic Factor / pharmacology
  • CREB-Binding Protein / physiology*
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Colforsin / pharmacology
  • Drug Interactions
  • Embryo, Mammalian
  • Gene Expression Regulation, Developmental / drug effects*
  • Green Fluorescent Proteins / biosynthesis
  • Green Fluorescent Proteins / genetics
  • Methyl-CpG-Binding Protein 2 / deficiency
  • Methyl-CpG-Binding Protein 2 / metabolism*
  • Mice
  • Mice, Knockout
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / pharmacology*
  • Neurons / drug effects
  • Oligonucleotides, Antisense / pharmacology
  • RNA, Small Interfering / pharmacology
  • Regulatory Elements, Transcriptional / genetics
  • Thionucleotides / pharmacology

Substances

  • Brain-Derived Neurotrophic Factor
  • Mecp2 protein, mouse
  • Methyl-CpG-Binding Protein 2
  • MicroRNAs
  • Oligonucleotides, Antisense
  • RNA, Small Interfering
  • Thionucleotides
  • Green Fluorescent Proteins
  • Colforsin
  • CREB-Binding Protein