title: 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 preadipocytes 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.
authors.affiliation: Institut de Genomique Fonctionnelle, Montpellier 34094, France; CNRS, UMR 5203, Montpellier 34094, France; INSERM, U661, Montpellier 34094, France; Faculté des Sciences, Université de Montpellier, Montpellier 34095, France;
authors.forename: Hala
authors.initials: H
authors.lastname: Al Adhami
authors.affiliation: Institut de Genomique Fonctionnelle, Montpellier 34094, France; CNRS, UMR 5203, Montpellier 34094, France; INSERM, U661, Montpellier 34094, France; Faculté des Sciences, Université de Montpellier, Montpellier 34095, France;
authors.forename: Brendan
authors.initials: B
authors.lastname: Evano
authors.affiliation: Institut de Genomique Fonctionnelle, Montpellier 34094, France; CNRS, UMR 5203, Montpellier 34094, France; INSERM, U661, Montpellier 34094, France; Faculté des Sciences, Université de Montpellier, Montpellier 34095, France;
authors.forename: Anne
authors.initials: A
authors.lastname: Le Digarcher
authors.affiliation: Institut de Genomique Fonctionnelle, Montpellier 34094, France; CNRS, UMR 5203, Montpellier 34094, France; INSERM, U661, Montpellier 34094, France; Faculté des Sciences, Université de Montpellier, Montpellier 34095, France;
authors.forename: Charlotte
authors.initials: C
authors.lastname: Gueydan
authors.affiliation: MGX-Montpellier GenomiX, Montpellier 34094, France.
authors.forename: Emeric
authors.initials: E
authors.lastname: Dubois
authors.affiliation: MGX-Montpellier GenomiX, Montpellier 34094, France.
authors.forename: Hugues
authors.initials: H
authors.lastname: Parrinello
authors.affiliation: MGX-Montpellier GenomiX, Montpellier 34094, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Dantec
authors.affiliation: Institut de Genomique Fonctionnelle, Montpellier 34094, France; CNRS, UMR 5203, Montpellier 34094, France; INSERM, U661, Montpellier 34094, France; Faculté des Sciences, Université de Montpellier, Montpellier 34095, France;
authors.forename: Tristan
authors.initials: T
authors.lastname: Bouschet
authors.affiliation: Institut de Genomique Fonctionnelle, Montpellier 34094, France; CNRS, UMR 5203, Montpellier 34094, France; INSERM, U661, Montpellier 34094, France; Faculté des Sciences, Université de Montpellier, Montpellier 34095, France;
authors.forename: Annie
authors.initials: A
authors.lastname: Varrault
authors.affiliation: Institut de Genomique Fonctionnelle, Montpellier 34094, France; CNRS, UMR 5203, Montpellier 34094, France; INSERM, U661, Montpellier 34094, France; Faculté des Sciences, Université de Montpellier, Montpellier 34095, France; MGX-Montpellier GenomiX, Montpellier 34094, France laurent.journot@igf.cnrs.fr.
authors.forename: Laurent
authors.identifier: http://orcid.org/0000-0003-3499-8887
authors.initials: L
authors.lastname: Journot
mesh_terms: D050156:Adipogenesis / Q000235:genetics; D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D019175:DNA Methylation; D030561:Databases, Nucleic Acid; D057890:Epigenomics / Q000379:methods*; D005109:Extracellular Matrix / Q000235:genetics; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D018392:Genomic Imprinting; D051379:Mice