Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA303156 | ENA |
REPOSITORIES: ENA
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Project description:Transcriptome analysis of postmortem brain samples frrom frontal and temporal cortex of Rett Syndrome cases and matched controls. These data identify genes differentially expressed in postmortem brain tissue from Rett Syndrome cases. Total RNA was extracted from 100mg of postmortem brain tissue.
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Project description:Transcriptome analysis of postmortem brain samples frrom frontal and temporal cortex of Rett Syndrome cases and matched controls. These data identify genes differentially expressed in postmortem brain tissue from Rett Syndrome cases.
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Project description:Rett syndrome is an X-linked neurodevelopmental disorder caused by mutation in the methyl-CpG-binding protein 2 gene in the majority of cases. We describe an RNA sequencing dataset of postmortem brain tissue samples from four females clinically diagnosed with Rett syndrome and four age-matched female donors. The dataset contains transcriptomes from two brain regions, temporal and cingulate cortex, for each individual, providing a valuable resource to explore the biology of the human brain in Rett syndrome.
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Project description:Epigenome analysis of Rett syndrome monozygotic twins samples
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Project description:We have sequenced miRNA libraries from human embryonic, neural and foetal mesenchymal stem cells. We report that the majority of miRNA genes encode mature isomers that vary in size by one or more bases at the 3’ and/or 5’ end of the miRNA. Northern blotting for individual miRNAs showed that the proportions of isomiRs expressed by a single miRNA gene often differ between cell and tissue types. IsomiRs were readily co-immunoprecipitated with Argonaute proteins in vivo and were active in luciferase assays, indicating that they are functional. Bioinformatics analysis predicts substantial differences in targeting between miRNAs with minor 5’ differences and in support of this we report that a 5’ isomiR-9-1 gained the ability to inhibit the expression of DNMT3B and NCAM2 but lost the ability to inhibit CDH1 in vitro. This result was confirmed by the use of isomiR-specific sponges. Our analysis of the miRGator database indicates that a small percentage of human miRNA genes express isomiRs as the dominant transcript in certain cell types and analysis of miRBase shows that 5’ isomiRs have replaced canonical miRNAs many times during evolution. This strongly indicates that isomiRs are of functional importance and have contributed to the evolution of miRNA genes
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Project description:Rett syndrome is a human intellectual disability disorder that is associated with mutations in the X-linked MECP2 gene. Theepigenetic reader MeCP2 binds to methylated cytosines on the DNA and regulates chromatin organization. We have shownpreviously that MECP2 Rett syndrome missense mutations are impaired in chromatin binding and heterochromatinreorganization. Here, we performed a proteomics analysis of post-translational modifications of MeCP2 isolated from adult mousebrain. We show that MeCP2 carries various post-translational modifications, among them phosphorylation on S80 and S421, whichlead to minor changes in either heterochromatin binding kinetics or clustering. We found that MeCP2 is (di)methylated on severalarginines and that this modification alters heterochromatin organization. Interestingly, we identified the Rett syndrome mutationsite R106 as a dimethylation site. In addition, co-expression of protein arginine methyltransferases 1 and 6 lead to a decrease ofheterochromatin clustering. Altogether, we identified and validated novel modifications of MeCP2 in the brain and show that thesecan modulate its ability to bind as well as reorganize heterochromatin, which may play a role in the pathology of Rett syndrome.
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Project description:Transcription profiling of cultured fibroblastic cell lines from Rett syndrome patients
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