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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 |
Authors: | 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. |
Issue 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 Institute of Clinical Sciences Faculty of Natural Sciences |