Transcriptome analysis of a MECP2 conditional KO mouse model
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ABSTRACT:
PROVIDER: PRJNA448674 | ENA |
REPOSITORIES: ENA
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Project description:Rett syndrome is a severe neurodevelopmental condition that rsults primarily from mutations in the MECP2 gene. MECP2 is known to function as both a transcriptional activator and transcriptional repressor. However, it remains unclear how transcriptional dysregulation resulting from MECP2 mutations lead to the Rett syndrome phenotype. Multiple mouse models have been generated to investigate the function of MECP2 in vivo. Remarkably, despite the neurodevelopmental phenotype characteristic of Rett syndrome, temporal conditional MECP2 knock-out mouse models with MECP2 deletion induced postnatally recapitulate the Rett-syndrome-like phenotype in mouse. Here we investigated gene expression changes in 22-weeks old mice following conditional MECP knock-out at 12 weeks by RNA-sequencing. Consistent with previous data, we identify mild gene expression changes following MECP2 knock-out. These data could prove valuable in future studies comparing conditional MECP2 knock-out at distinct time points and in additional brain regions, and can also serve for investigating alternative splicing changes resulting from MECP2 conditional deletion.
2018-04-05 | GSE112663 | GEO
Project description:We report the application of genome-wide RNA-sequencing analysis for Esrrb WT and conditional Esrrb KO mES cells after differentation for 48 hours. Global transcriptome profiling revealed impaired induction of formative genes in conditional KO cells compared to WT cells.
2023-01-25 | GSE217802 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE24285: Genome-wide Analysis Reveals Mecp2-dependent Regulation of MicroRNAs in a Mouse Model of Rett Syndrome (mm8 chromosomal tiling arrays) GSE24286: Genome-wide Analysis Reveals Mecp2-dependent Regulation of MicroRNAs in a Mouse Model of Rett Syndrome (mm8 promoter tiling arrays) GSE24320: Genome-wide Analysis Reveals Mecp2-dependent Regulation of MicroRNAs in a Mouse Model of Rett Syndrome (high-throughput small RNA sequencing) Refer to individual Series
2010-09-29 | E-GEOD-24329 | biostudies-arrayexpress
Project description:The goal of this study is to investigate the transcriptional network regulated by DIAPH3 gene (mDia2) using the conditional hematopoietic specific knockout mouse model, especially in the cell proliferation, cell survive (including oxidative stress), cell adhesion & migration, cell cycle and hematopoiesis pathway-related genes. Two groups of mice (WT vs KO) were sacrificed to purify erythroblast (Ter119+) cells from total bone marrow for RNA preparation. Each group contains three mice, the WT group includes 917,1125,1136 and 907,914,1122 belong to the conditional KO group. There is biological triplication in each group.
2015-04-30 | E-GEOD-68422 | biostudies-arrayexpress
Project description:MicroRNAs (miRNAs) are a class of small non-coding RNAs that function as post-transcriptional regulators of gene expression. Many miRNAs are expressed in the developing brain and regulate multiple aspects of neural development including neurogenesis, dendritogenesis and synapse formation. Rett syndrome (RTT) is a progressive neurodevelopmental disorder caused by mutations in the gene encoding Methyl-CpG binding protein 2 (MECP2). While Mecp2 is known to act as a global transcriptional regulator, miRNAs that are directly regulated by Mecp2 in the brain are not known. Using massively parallel sequencing methods, we have identified miRNAs whose expression is altered in cerebella of Mecp2-null mice before and after the onset of severe neurological symptoms. In vivo genome-wide analyses indicate that promoter regions of a significant fraction of dys-regulated miRNA transcripts, including a large polycistronic cluster of brain-specific miRNAs, are DNA methylated and directly bound by Mecp2. Functional analysis demonstrates that the 3’ untranslated region (UTR) of messenger RNA encoding Brain-derived neurotrophic factor (Bdnf) can be targeted by multiple miRNAs aberrantly up-regulated in absence of Mecp2. Taken together, these results suggest that dys-regulation of miRNAs may contribute to RTT pathoetiology, and also provide a valuable resource to further investigate the role of miRNAs in RTT. Two pooled total RNA samples (4 pairs of wild-type (WT) and Mecp2-null (KO) male mice; postnatal 6-week, the pre-/early-symptomatic stage) were sequenced in a multiplexed configuration (with distinct barcode sequences). And, six samples (two litters, one WT and two KO male mice in each litter; postnatal 8-week, the symptomatic stage) were sequenced individually.
2010-09-29 | E-GEOD-24320 | biostudies-arrayexpress
Project description:MicroRNAs (miRNAs) are a class of small non-coding RNAs that function as post-transcriptional regulators of gene expression. Many miRNAs are expressed in the developing brain and regulate multiple aspects of neural development including neurogenesis, dendritogenesis and synapse formation. Rett syndrome (RTT) is a progressive neurodevelopmental disorder caused by mutations in the gene encoding Methyl-CpG binding protein 2 (MECP2). While Mecp2 is known to act as a global transcriptional regulator, miRNAs that are directly regulated by Mecp2 in the brain are not known. Using massively parallel sequencing methods, we have identified miRNAs whose expression is altered in cerebella of Mecp2-null mice before and after the onset of severe neurological symptoms. In vivo genome-wide analyses indicate that promoter regions of a significant fraction of dys-regulated miRNA transcripts, including a large polycistronic cluster of brain-specific miRNAs, are DNA methylated and directly bound by Mecp2. Functional analysis demonstrates that the 3’ untranslated region (UTR) of messenger RNA encoding Brain-derived neurotrophic factor (Bdnf) can be targeted by multiple miRNAs aberrantly up-regulated in absence of Mecp2. Taken together, these results suggest that dys-regulation of miRNAs may contribute to RTT pathoetiology, and also provide a valuable resource to further investigate the role of miRNAs in RTT. Chromatin extracted from postnatal 6-8 week old cerebellar (CB) tissues of wild-type (WT) or Mecp2-null (KO) male mice was immunoprecipitated with indicated antibodies and analyzed by a NimbleGen mouse 385K genomic tiling microarray (the array set26 of a 37-array set, which covers the mouse chromosome 12 that includes the entire Dlk1-Gtl2 imprinting domain). Whole cell extract (WCE) was used as input controls for ChIP or MeDIP/WCE experiments. For ChIP/ChIP experiments, immunoprecipitated DNA from WT and KO CB was directly compared on the same microarrays. DNA methylation profiles in WT CB were also analyzed by methylated DNA immunoprecipitation (MeDIP) followed by hybridization to the same genomic tiling microarrays (MeDIP-chip).
2010-09-30 | E-GEOD-24285 | biostudies-arrayexpress
Project description:We investigated whether dietary vitamin D supplementation can rescue the expression of genes that are dysregulated within the neocortex of Mecp2+/- mice, and whether vitamin D deficiency further exacerbates transcriptome disruptions in these mice. We found that dietary vitamin D modification has a profound impact on the transcriptome of the neocortex. We identified more than 200 differentially expressed genes whose expression is normalized with vitamin D supplementation, many of which are associated with neuronal morphology. Dietary vitamin D deficiency exacerbated the dysregulation of many of these genes in the Mecp2+/- cortex, but, strikingly, it normalized the expression of many other dysregulated genes, similar to the effect of supplementation.
2022-01-31 | GSE180630 | GEO
Project description: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. 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.
2008-05-30 | E-GEOD-11596 | biostudies-arrayexpress
Project description:Rett syndrome (RTT) is an X-linked neurodevelopmental disorder caused by mutations in the transcriptional regulator MeCP2. RTT is characterized by having apparently normal development until 6-18 months, when a progressive decline in motor and language functions begins and breathing abnormalities and seizures present. Here we present the first proteomic analysis in a RTT mouse model. Examining whole cortex tissue in symptomatic males (Mecp2Jae/y) and wild-type littermates, we have identified 465 proteins significantly altered. Pathway analysis identified biological pathways ubiquitous to multiple cell types as well as cell type specific pathways, underscoring the contributions of multiple central nervous system (CNS) cell populations to the disease pathogenesis.
2017-11-02 | PXD006460 | Pride
Project description:MicroRNAs (miRNAs) are a class of small non-coding RNAs that function as post-transcriptional regulators of gene expression. Many miRNAs are expressed in the developing brain and regulate multiple aspects of neural development including neurogenesis, dendritogenesis and synapse formation. Rett syndrome (RTT) is a progressive neurodevelopmental disorder caused by mutations in the gene encoding Methyl-CpG binding protein 2 (MECP2). While Mecp2 is known to act as a global transcriptional regulator, miRNAs that are directly regulated by Mecp2 in the brain are not known. Using massively parallel sequencing methods, we have identified miRNAs whose expression is altered in cerebella of Mecp2-null mice before and after the onset of severe neurological symptoms. In vivo genome-wide analyses indicate that promoter regions of a significant fraction of dys-regulated miRNA transcripts, including a large polycistronic cluster of brain-specific miRNAs, are DNA methylated and directly bound by Mecp2. Functional analysis demonstrates that the 3’ untranslated region (UTR) of messenger RNA encoding Brain-derived neurotrophic factor (Bdnf) can be targeted by multiple miRNAs aberrantly up-regulated in absence of Mecp2. Taken together, these results suggest that dys-regulation of miRNAs may contribute to RTT pathoetiology, and also provide a valuable resource to further investigate the role of miRNAs in RTT. Chromatin extracted from postnatal 6-8 week old cerebellar (CB) tissues of wild-type (WT) or Mecp2-null (KO) male mice was immunoprecipitated with indicated antibodies and analyzed by NimbleGen custom mouse 385K promoter tiling microarrays (a 2-array set covering the promoter regions of all Refseq protein-coding genes and miRNA transcripts with predicted transcription start sites). Whole cell extract (WCE) was used as input controls in all experiments. DNA methylation profiles in WT CB were also analyzed by methylated DNA immunoprecipitation (MeDIP) followed by hybridization to the same promoter tiling microarrays (MeDIP-chip).
2010-09-30 | E-GEOD-24286 | biostudies-arrayexpress