Human Molecular Genetics Advance Access originally published online on January 18, 2008
Human Molecular Genetics 2008 17(8):1192-1199; doi:10.1093/hmg/ddn011
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MeCP2-dependent repression of an imprinted miR-184 released by depolarization
1 Laboratory of Genome Science, Biosignal Genome Resource Center, Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-machi, Maebashi 371-8512, Japan 2 Division of Molecular Biology and Genetics, Department of Biomolecular Sciences, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan 3 Hokkaido Institute of Public Health, Kita-19, Nishi-12, Kita-ku, Sapporo 060-0819, Japan
* To whom correspondence should be addressed. Tel: + 81 272208057; Fax: + 81 27 2208110; Email: ihatada{at}showa.gunma-u.ac.jp
Received August 21, 2007; Revised November 11, 2007; Accepted January 16, 2008
Both fragile X syndrome and Rett syndrome are commonly associated with autism spectrum disorders and involve defects in synaptic plasticity. MicroRNA is implicated in synaptic plasticity because fragile X mental retardation protein was recently linked to the microRNA pathway. DNA methylation is also involved in synaptic plasticity since methyl CpG-binding protein 2 (MeCP2) is mutated in patients with Rett syndrome. Here we report that expression of miR-184, a brain-specific microRNA repressed by the binding of MeCP2 to its promoter, is upregulated by the release of MeCP2 after depolarization. The restricted release of MeCP2 from the paternal allele results in paternal allele-specific expression of miR-184. Our finding provides a clue to the link between the microRNA and DNA methylation pathways.