MeCP2 is involved in random mono-allelic expression for a subset of human autosomal genes
| Autor: | Thierry Bienvenu, Franck Letourneur, Emmanuelle Olivier, Benjamin Saintpierre, Brigitte Izac, Marine Brousseau, Nicolas Cagnard, Juliette Nectoux, Nicolas Lebrun |
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| Přispěvatelé: | Service de biochimie et de génétique moléculaire [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), U 1016/ UMR 8104 Institut Cochin, Plate-Forme Séquençage et Génomique (Genom'IC), Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Plateforme de Bioinformatique [Paris] (Fondation Imagine), Martinez Rico, Clara, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
congenital hereditary and neonatal diseases and abnormalities Methyl-CpG-Binding Protein 2 [SDV]Life Sciences [q-bio] Mutant Rett syndrome Biology Allelic Imbalance MECP2 03 medical and health sciences 0302 clinical medicine Genes X-Linked Gene expression mental disorders medicine [SDV.BBM] Life Sciences [q-bio]/Biochemistry Molecular Biology Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Allele Molecular Biology Gene Alleles Genetics [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology medicine.disease nervous system diseases [SDV] Life Sciences [q-bio] 030104 developmental biology Phenotype Gene Expression Regulation Mono-allelic expression Mutation Molecular Medicine Human genome Genomic imprinting 030217 neurology & neurosurgery [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology |
| Zdroj: | Biochimica et Biophysica Acta-Molecular Basis of Disease Biochimica et Biophysica Acta-Molecular Basis of Disease, Elsevier, 2020, 1866 (6), pp.165730. ⟨10.1016/j.bbadis.2020.165730⟩ |
| ISSN: | 0925-4439 |
| DOI: | 10.1016/j.bbadis.2020.165730⟩ |
| Popis: | International audience; Widespread 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 expression of at least 49 genes allowing us to define a specific signature of MECP2 mutated clones. |
| Databáze: | OpenAIRE |
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