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Visualizing Changes in Cdkn1c Expression Links Early-Life Adversity to Imprint Mis-regulation in Adults.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Van de Pette, Mathew 
Abbas, Allifia 
Feytout, Amelie 
McNamara, Gráinne 
Bruno, Ludovica 

Abstract

Imprinted genes are regulated according to parental origin and can influence embryonic growth and metabolism and confer disease susceptibility. Here, we designed sensitive allele-specific reporters to non-invasively monitor imprinted Cdkn1c expression in mice and showed that expression was modulated by environmental factors encountered in utero. Acute exposure to chromatin-modifying drugs resulted in de-repression of paternally inherited (silent) Cdkn1c alleles in embryos that was temporary and resolved after birth. In contrast, deprivation of maternal dietary protein in utero provoked permanent de-repression of imprinted Cdkn1c expression that was sustained into adulthood and occurred through a folate-dependent mechanism of DNA methylation loss. Given the function of imprinted genes in regulating behavior and metabolic processes in adults, these results establish imprinting deregulation as a credible mechanism linking early-life adversity to later-life outcomes. Furthermore, Cdkn1c-luciferase mice offer non-invasive tools to identify factors that disrupt epigenetic processes and strategies to limit their long-term impact.

Description

Keywords

Cdkn1c, bioluminescence, environmental stress, imprinting, luciferase reporter mice, Alleles, Animals, Chromatin, Cyclin-Dependent Kinase Inhibitor p57, DNA Methylation, Epigenesis, Genetic, Genomic Imprinting, Mice

Journal Title

Cell Rep

Conference Name

Journal ISSN

2211-1247
2211-1247

Volume Title

18

Publisher

Elsevier BV
Sponsorship
Wellcome Trust (095606/Z/11/Z)