MeCP2, a Key Contributor to Neurological Disease, Activates and Represses Transcription
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- 30 May 2008
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 320 (5880) , 1224-1229
- https://doi.org/10.1126/science.1153252
Abstract
Mutations in the gene encoding the transcriptional repressor methyl-CpG binding protein 2 (MeCP2) cause the neurodevelopmental disorder Rett syndrome. Loss of function as well as increased dosage of theMECP2gene cause a host of neuropsychiatric disorders. To explore the molecular mechanism(s) underlying these disorders, we examined gene expression patterns in the hypothalamus of mice that either lack or overexpress MeCP2. In both models, MeCP2 dysfunction induced changes in the expression levels of thousands of genes, but unexpectedly the majority of genes (∼85%) appeared to be activated by MeCP2. We selected six genes and confirmed that MeCP2 binds to their promoters. Furthermore, we showed that MeCP2 associates with the transcriptional activator CREB1 at the promoter of an activated target but not a repressed target. These studies suggest that MeCP2 regulates the expression of a wide range of genes in the hypothalamus and that it can function as both an activator and a repressor of transcription.Keywords
This publication has 22 references indexed in Scilit:
- Brain-Specific Phosphorylation of MeCP2 Regulates Activity-Dependent Bdnf Transcription, Dendritic Growth, and Spine MaturationNeuron, 2006
- Pediatric Autonomic DisordersPediatrics, 2006
- MeCP2 dysfunction in Rett syndrome and related disordersCurrent Opinion in Genetics & Development, 2006
- The Disease Progression of Mecp2 Mutant Mice Is Affected by the Level of BDNF ExpressionNeuron, 2006
- Detection and measurement of alternative splicing using splicing-sensitive microarraysMethods, 2005
- Guanidinoacetate methyltransferase deficiency identified in adults and a child with mental retardationAmerican Journal of Medical Genetics Part A, 2005
- Biochemical and clinical characteristics of creatine deficiency syndromes.Acta Biochimica Polonica, 2004
- Mild overexpression of MeCP2 causes a progressive neurological disorder in miceHuman Molecular Genetics, 2004
- Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2Nature Genetics, 1999
- Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complexNature, 1998