Maternal programming of steroid receptor expression and phenotype through DNA methylation in the rat.
Increased levels of pup licking/grooming and arched-back nursing by rat mothers over the first week of life alter the epigenome at a glucocorticoid receptor gene promoter in the hippocampus of the offspring. Differences in the DNA methylation pattern between the offspring of High and Low licking/grooming--arched-back mothers emerge over the first week of life, are reversed with cross-fostering, persist into adulthood and are associated with altered histone acetylation and transcription factor (NGFI-A) binding to the glucocorticoid receptor promoter. Central infusion of the adult offspring with the histone deacetylase inhibitor trichostatin A removes the previously defined epigenomic group differences in histone acetylation, DNA methylation, NGFI-A binding, glucocorticoid receptor expression, and hypothalamic-pituitary-adrenal responses to stress, thus suggesting a causal relation between the epigenomic state, glucocorticoid receptor expression and the effects of maternal care on stress responses in the offspring. These findings demonstrate that an epigenomic state of a gene can be established through a behavioral mode of programming and that in spite of the inherent stability of this epigenomic mark, it is dynamic and potentially reversible.
Szyf
Moshe
M
McGill Program for the Study of Behavior, Genes and Environment, McGill University, Montreal, Canada.
Weaver
Ian C G
IC
Champagne
Francis A
FA
Diorio
Josie
J
Meaney
Michael J
MJ
D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D005786:Gene Expression Regulation; D006120:Grooming / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism; D007398:Interpersonal Relations; D008297:Male; D008425:Maternal Behavior; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000502:physiology; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000235:genetics* / Q000378:metabolism; D013315:Stress, Psychological / Q000235:genetics*
D011965:Receptors, Glucocorticoid; D003346:Corticotropin-Releasing Hormone