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A systems-level approach to parental genomic imprinting: the imprinted gene network includes extracellular matrix genes and regulates cell cycle exit and differentiation

Abstract : Genomic imprinting is an epigenetic mechanism that restrains the expression of~100 eutherian genes in a parent-of-origin-specific manner. The reason for this selective targeting of genes with seemingly disparate molecular functions is unclear. In the present work, we show that imprinted genes are coexpressed in a network that is regulated at the transition from proliferation to quiescence and differentiation during fibroblast cell cycle withdrawal, adipogenesis in vitro, and muscle regeneration in vivo. Imprinted gene regulation is not linked to alteration of DNA methylation or to perturbation of monoallelic, parent-of-origin-dependent expression. Overexpression and knockdown of imprinted gene expression alters the sensitivity of pre-adipocytes to contact inhibition and adipogenic differentiation. In silico and in cellulo experiments showed that the imprinted gene network includes biallelically expressed, nonimprinted genes. These control the extracellular matrix composition, cell adhesion, cell junction, and extracellular matrix-activated and growth factor-activated signaling. These observations show that imprinted genes share a common biological process that may account for their seemingly diverse roles in embryonic development, obesity, diabetes, muscle physiology, and neoplasm.
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https://hal.umontpellier.fr/hal-01788711
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Soumis le : jeudi 12 mars 2020 - 11:55:52
Dernière modification le : vendredi 13 mars 2020 - 14:20:28

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Hala Al Adhami, Brendan Evano, Anne Le Digarcher, Charlotte Gueydan, Emeric Dubois, et al.. A systems-level approach to parental genomic imprinting: the imprinted gene network includes extracellular matrix genes and regulates cell cycle exit and differentiation. Genome Research, Cold Spring Harbor Laboratory Press, 2015, 25 (3), pp.353 - 367. ⟨10.1101/gr.175919.114⟩. ⟨hal-01788711⟩

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