Genome-wide Analysis Reveals Mecp2-dependent Regulation of MicroRNAs in a Mouse Model of Rett Syndrome
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE24329 | GEO | 2010/09/30
SECONDARY ACCESSION(S): PRJNA132739
REPOSITORIES: GEO
Similar Datasets
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: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: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
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.
2010-09-30 | GSE24285 | GEO
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.
2010-09-30 | GSE24320 | GEO
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.
2010-09-30 | GSE24286 | GEO
Project description:MicroRNAs (miRNAs) are a class of small, noncoding RNAs that function as posttranscriptional 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). Although 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 dysregulated miRNA transcripts, including a large polycistronic cluster of brain-specific miRNAs, are DNA-methylated and are bound directly by Mecp2. Functional analysis demonstrates that the 3' UTR of messenger RNA encoding Brain-derived neurotrophic factor (Bdnf) can be targeted by multiple miRNAs aberrantly up-regulated in the absence of Mecp2. Taken together, these results suggest that dysregulation of miRNAs may contribute to RTT pathoetiology and also may provide a valuable resource for further investigations of the role of miRNAs in RTT.
| S-EPMC2964235 | biostudies-literature
Project description:Rett syndrome (RTT) is a severe and progressive neurological disorder, which mainly affects young females. Mutations of the methyl-CpG binding protein 2 (MECP2) gene are the most prevalent cause of classical RTT cases. MECP2 mutations or altered expression are also associated with a spectrum of neurodevelopmental disorders such as autism spectrum disorders with recent links to fetal alcohol spectrum disorders. Collectively, MeCP2 relation to these neurodevelopmental disorders highlights the importance of understanding the molecular mechanisms by which MeCP2 impacts brain development, mental conditions, and compromised brain function. Since MECP2 mutations were discovered to be the primary cause of RTT, a significant progress has been made in the MeCP2 research, with respect to the expression, function and regulation of MeCP2 in the brain and its contribution in RTT pathogenesis. To date, there have been intensive efforts in designing effective therapeutic strategies for RTT benefiting from mouse models and cells collected from RTT patients. Despite significant progress in MeCP2 research over the last few decades, there is still a knowledge gap between the in vitro and in vivo research findings and translating these findings into effective therapeutic interventions in human RTT patients. In this review, we will provide a synopsis of Rett syndrome as a severe neurological disorder and will discuss the role of MeCP2 in RTT pathophysiology.
| S-EPMC5798978 | biostudies-literature
Project description:Methyl-CpG-binding protein 2 (MeCP2) epigenetically modulates gene expression through genome-wide binding to methylated CpG dinucleotides. This study aimed to evaluate the effect of MeCP2 on the global gene expression profile of human gastric adenocarcinoma to determine the potential molecular mechanism of MeCP2. To identify the gene targets of MeCP2 in gastric cancer cells, we combined the expression microarray and chromatin immunoprecipitation approaches of MeCP2, followed by sequencing (ChIP-seq) to define the MeCP2-binding sites across the whole genome. The methylation levels of the promoters in BGC-823 cells were downloaded from the National Center for Biotechnology Information Gene Expression Omnibus database (GSM1093053). A total of 5,684 ChIP-enriched peaks were identified by comparing IP and Input, using a p-value threshold of 10-5 in ChIP-seq. The bioinformatics analysis presented a predictive model of the genome-wide MeCP2-binding pattern, in which the MeCP2 binding site is closely related to the transcription start site region in the genome. The results of motif detection showed that the MeCP2-binding regions contained not only the core CpG motif but also the extended poly (A/T) motifs. Finally, an integrative analysis of the sequence features and DNA methylation states revealed that MeCP2's function as a multifunctional transcriptional regulator may not be directly related to the methylation status of the binding site. The first MeCP2 ChIP-seq and gene expression microarray analysis in BGC-823 cells revealed that MeCP2 plays multiple roles in the regulation of gene expression depending on the microenvironment, such as sequence characteristics and the methylation levels of binding sites.
| S-EPMC7414497 | biostudies-literature