Visualizing changes in Cdkn1c expression links early life adversity to imprint mis-regulation in adults

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Title: Visualizing changes in Cdkn1c expression links early life adversity to imprint mis-regulation in adults
Author(s): Van de Pette, M
Abbas, A
Feytout, A
McNamara, G
Bruno, L
To, WK
Dimond, A
Sardini, A
Webster, Z
McGinty, J
Paul, EJ
Ungless, MA
French, PMW
Withers, DJ
Uren, A
Ferguson-Smith, AC
Merkenschlager, M
John, RM
Fisher, AG
Item Type: Journal Article
Abstract: Imprinted genes are regulated accordin g 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 l oss . 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.
Publication Date: 31-Jan-2017
Date of Acceptance: 7-Jan-2017
URI: http://hdl.handle.net/10044/1/43828
DOI: https://dx.doi.org/10.1016/j.celrep.2017.01.010
ISSN: 2211-1247
Publisher: Elsevier (Cell Press)
Start Page: 1090
End Page: 1099
Journal / Book Title: Cell Reports
Volume: 31
Issue: 5
Copyright Statement: © 2017 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
Sponsor/Funder: Commission of the European Communities
Wellcome Trust
Wellcome Trust
Imperial College Trust
Funder's Grant Number: 294627
097816/Z/11/B
105603/Z/14/Z
n/a
Keywords: Science & Technology
Life Sciences & Biomedicine
Cell Biology
BECKWITH-WIEDEMANN-SYNDROME
DEPENDENT KINASE INHIBITOR
MOUSE DISTAL CHROMOSOME-7
STEM-CELLS
DNA METHYLATION
P57(KIP2)
GENE
DOMAIN
MODEL
MAINTENANCE
Cdkn1c
bioluminescence
environmental stress
imprinting
luciferase reporter mice
Publication Status: Published
Appears in Collections:Physics
Photonics
Clinical Sciences
Molecular Sciences
Faculty of Medicine
Faculty of Natural Sciences



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