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Locus specific epigenetic modalities of random allelic expression imbalance

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Item Type:Article
Title:Locus specific epigenetic modalities of random allelic expression imbalance
Creators Name:Marion-Poll, L. and Forêt, B. and Zielinski, D. and Massip, F. and Attia, M. and Carter, A.C. and Syx, L. and Chang, H.Y. and Gendrel, A.V. and Heard, E.
Abstract:Most autosomal genes are thought to be expressed from both alleles, with some notable exceptions, including imprinted genes and genes showing random monoallelic expression (RME). The extent and nature of RME has been the subject of debate. Here we investigate the expression of several candidate RME genes in F1 hybrid mouse cells before and after differentiation, to define how they become persistently, monoallelically expressed. Clonal monoallelic expression is not present in embryonic stem cells, but we observe high frequencies of monoallelism in neuronal progenitor cells by assessing expression status in more than 200 clones. We uncover unforeseen modes of allelic expression that appear to be gene-specific and epigenetically regulated. This non-canonical allelic regulation has important implications for development and disease, including autosomal dominant disorders and opens up therapeutic perspectives.
Keywords:Acid Anhydride Hydrolases, Alleles, Allelic Imbalance, Animal Disease Models, Apoptosis Regulatory Proteins, Cell Differentiation, Chimera, Clone Cells, DNA Methylation, DNA-Binding Proteins, Genetic Epigenesis, Gene Dosage, Gene Frequency, Genetic Loci, Genomic Imprinting, Kainic Acid Receptors, Muscular Diseases, Neoplasms, Neural Stem Cells, Neurodegenerative Diseases, Osteoporosis, Signal Transducing Adaptor Proteins, Animals, Mice
Source:Nature Communications
Publisher:Nature Publishing Group
Page Range:5330
Date:9 September 2021
Official Publication:https://doi.org/10.1038/s41467-021-25630-3
PubMed:View item in PubMed

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