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Genome Res. 2015 Mar;25(3):353-67. doi: 10.1101/gr.175919.114. Epub 2015 Jan 22.

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

Author information

1
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;
2
MGX-Montpellier GenomiX, Montpellier 34094, France.
3
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.

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.

PMID:
25614607
PMCID:
PMC4352888
DOI:
10.1101/gr.175919.114
[Indexed for MEDLINE]
Free PMC Article

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