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Gene expression profiles of wild type and Mecp2-null mice in three different regions of the brain

ABSTRACT: Background. Rett syndrome (RTT) is a complex neurodevelopmental disorder that is one of the most frequent causes of mental retardation in women. A great landmark in research in this field was the discovery of a relationship between the disease and the presence of mutations in the gene that codes for the methyl-CpG binding protein 2 (MeCP2). Currently, MeCP2 is thought to act as a transcriptional repressor that couples DNA methylation and transcriptional silencing. The present study aimed to identify new target genes directly regulated by Mecp2 in a mouse model of RTT. Methodology. We have compared the gene expression profiles of wild type (WT) and Mecp2-null (KO) mice in three regions of the brain (cortex, midbrain, and cerebellum) by using cDNA microarrays. The results obtained were confirmed by quantitative real-time PCR. Subsequent chromatin immunoprecipitation assays revealed seven direct target genes of Mecp2 bound in vivo (Dlk1, Mobp, Plagl1, Ddc, Mllt2h, Eya2, and S100a9), and two overexpressed genes due to an indirect effect of a lack of Mecp2 (Irak1 and Prodh). Bisulfite sequencing analysis of the methylation patterns of promoters of the described genes showed no differences between WT and KO mice, demonstrating that methylation differences were not the cause of the observed expression changes. Moreover, the regions bound by Mecp2 were always methylated, suggesting the involvement of the methyl-CpG binding domain of the protein in the mechanism of interaction. Conclusions. We identified new genes that are overexpressed in KO mice and are excellent candidate genes for involvement in various features of the neurodevelopmental disease. Our results demonstrate new targets of MeCP2 and provide us with a better understanding of the underlying mechanisms of RTT. Overall design: Comparative experiment: Mecp2-null (KO) mice vs. their corresponding age-mated wild type (WT) littermates (CONTROLS). Four couples of KO-WT animals are used and three different brain regions are studied from each couple; cortex, midbrain, and cerebellum.

INSTRUMENT(S): CNIO Mouse chip 27.6K 3.0

ORGANISM(S): Mus musculus  

SUBMITTER: Rocio G. Urdinguio  

PROVIDER: GSE11596 | GEO | 2008-05-31



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