MeCP2 is involved in random mono-allelic expression for a subset of human autosomal genes

Publication date: Available online 15 February 2020Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Marine Brousseau, Juliette Nectoux, Benjamin Saintpierre, Nicolas Lebrun, Nicolas Cagnard, Brigitte Izac, Emmanuelle Olivier, Franck Letourneur, Thierry BienvenuAbstractWidespread random monoallelic gene expression (RMAE) effects influence about 10% of human genes. However, the mechanisms by which RME of autosomal genes is established and those by which it is maintained both remain open questions. Because the choice of allelic expression is randomly performed cell-by-cell, the RMAE mechanism is not observable in non-clonal cell populations or in whole tissues. Several target genes of MeCP2, the gene involved in Rett syndrome (RTT), have been previously described as subject to RMAE, suggesting that MeCP2 may be involved in the establishment and/or maintenance of RME of autosomal genes. To improve our knowledge on this largely unknown phenomenon, and to study the role of MeCP2 in RMAE, we compared RMA gene expression profiles in clonal cell cultures expressing wild-type MeCP2 versus mutant MeCP2 from a RTT patient carrying a pathogenic non-sense variant. Our data clearly demonstrated that MeCP2 deficiency does not affect significantly allelic gene expression of X-linked genes, imprinted genes as well as the RMAE profile in the majority of genes. However, the functional deficiency in MeCP2 appeared to disrupt the mono-allelic or the bi-allelic exp...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research

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Publication date: 24 March 2020Source: Cell Reports, Volume 30, Issue 12Author(s): Deivid C. Rodrigues, Marat Mufteev, Robert J. Weatheritt, Ugljesa Djuric, Kevin C.H. Ha, P. Joel Ross, Wei Wei, Alina Piekna, Maria A. Sartori, Loryn Byres, Rebecca S.F. Mok, Kirill Zaslavsky, Peter Pasceri, Phedias Diamandis, Quaid Morris, Benjamin J. Blencowe, James Ellis
Source: Cell Reports - Category: Cytology Source Type: research
Abstract Structural Maintenance of Chromosomes (SMCs) are part of a large family of ring complexes that participates in a number of DNA transactions. Among SMCs, SMC1A gene is unique. It encodes a subunit of the cohesin-core complex that tethers sister chromatids together to ensure correct chromosome segregation in both mitosis and meiosis. As a member of the cohesin ring, SMC1A takes part in gene transcription regulation and genome organization; and it participates in the DNA Damage Repair (DDR) pathway, being phosphorylated by Ataxia Telangiectasia Mutated (ATM) and Ataxia Telangiectasia and Rad3 Related (ATR) t...
Source: Gene - Category: Genetics & Stem Cells Authors: Tags: Gene Source Type: research
Rett syndrome is an incurable neurodevelopmental disorder caused by mutations in the gene encoding for methyl-CpG binding-protein 2 (MeCP2). Gene therapy for this disease presents inherent hurdles sinceMECP2 is expressed throughout the brain and its duplication leads to severe neurological conditions as well. Herein, we use the AAV-PHP.eB to deliver an instability-proneMecp2 (iMecp2) transgene cassette which, increasing RNA destabilization and inefficient protein translation of the viralMecp2transgene, limits supraphysiological Mecp2 protein levels. Intravenous injections of the PHP.eB-iMecp2 virus in symptomaticMecp2 muta...
Source: eLife - Category: Biomedical Science Tags: Neuroscience Source Type: research
Authors: Provvidenziale L, Cinotti E, Campoli M, Russo F, Rubegni P PMID: 32163043 [PubMed - as supplied by publisher]
Source: Giornale Italiano di Dermatologia e Venereologia - Category: Dermatology Tags: G Ital Dermatol Venereol Source Type: research
Condition:   Rett Syndrome Interventions:   Drug: ANAVEX2-73 oral liquid;   Drug: Placebo oral liquid Sponsors:   Anavex Life Sciences Corp.;   Anavex Australia Pty Ltd.;   Anavex Germany GmbH Recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Methylated cytosine is an effector of epigenetic gene regulation. In the brain, Dnmt3a is the sole ‘writer’ of atypical non-CpG methylation (mCH), and MeCP2 is the only known ‘reader’ for mCH. We asked if MeCP2 is the sole reader for Dnmt3a dependent methylation by comparing mice lacking either protein in GABAergic inhibitory neurons. Loss of either protein causes overlapping and distinct features from the behavioral to molecular level. Loss of Dnmt3a causes global loss of mCH and a subset of mCG sites resulting in more widespread transcriptional alterations and severe neurological dysfunction than ...
Source: eLife - Category: Biomedical Science Tags: Chromosomes and Gene Expression Neuroscience Source Type: research
No abstract available
Source: Clinical Dysmorphology - Category: Genetics & Stem Cells Tags: Short Case Reports Source Type: research
Conclusion Our study showed sleep dysfunction to be less prevalent in RTT-affected individuals than evidence from past studies has suggested. Nevertheless, this remains a subjective assessment of sleep quality and therefore the need to find objective, disorder-specific parameters that measure sleep quality in RTT patients persists. [...] Georg Thieme Verlag KG Stuttgart · New YorkArticle in Thieme eJournals: Table of contents  |  Abstract  |  Full text
Source: Neuropediatrics - Category: Neurology Authors: Tags: Original Article Source Type: research
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