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

Mathew Van de Pette | Zendy; Allifia Abbas | Zendy; Amélie Feytout | Zendy; Gráinne I. McNamara | Zendy; Ludovica Bruno | Zendy; Wilson To | Zendy; Andrew Dimond | Zendy; Alessandro Sardini | Zendy; Zoë Webster | Zendy; James McGinty | Zendy; Eleanor J. Paul | Zendy; Mark A. Ungless | Zendy; P. M. W. French | Zendy; Dominic J. Withers | Zendy; Anthony G. Uren | Zendy; Anne C. FergusonSmith | Zendy; Matthias Merkenschlager | Zendy; Rosalind M. John | Zendy; Amanda G. Fisher | Zendy

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

Author(s) -

Mathew Van de Pette,

Allifia Abbas,

Amélie Feytout,

Gráinne I. McNamara,

Ludovica Bruno,

Wilson To,

Andrew Dimond,

Alessandro Sardini,

Zoë Webster,

James McGinty,

Eleanor J. Paul,

Mark A. Ungless,

P. M. W. French,

Dominic J. Withers,

Anthony G. Uren,

Anne C. FergusonSmith,

Matthias Merkenschlager,

Rosalind M. John,

Amanda G. Fisher

Publication year - 2017

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2017.01.010

Subject(s) - genomic imprinting , epigenetics , imprinting (psychology) , dna methylation , biology , psychological repression , allele , genetics , regulation of gene expression , chromatin , in utero , mechanism (biology) , gene expression , gene , fetus , pregnancy , philosophy , epistemology

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.

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