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.