Epigenetic programming by maternal behavior.
Here we report that increased pup licking and grooming (LG) and arched-back nursing (ABN) by rat mothers altered the offspring epigenome at a glucocorticoid receptor (GR) gene promoter in the hippocampus. Offspring of mothers that showed high levels of LG and ABN were found to have differences in DNA methylation, as compared to offspring of 'low-LG-ABN' mothers. These differences emerged over the first week of life, were reversed with cross-fostering, persisted into adulthood and were associated with altered histone acetylation and transcription factor (NGFI-A) binding to the GR promoter. Central infusion of a histone deacetylase inhibitor removed the group differences in histone acetylation, DNA methylation, NGFI-A binding, GR expression and hypothalamic-pituitary-adrenal (HPA) responses to stress, suggesting a causal relation among epigenomic state, GR expression and the maternal effect on stress responses in the offspring. Thus we show that an epigenomic state of a gene can be established through behavioral programming, and it is potentially reversible.
Weaver
Ian C G
IC
Douglas Hospital Research Center, 6875 LaSalle Blvd., Montréal, Québec H4H 1R3, Canada.
Cervoni
Nadia
N
Champagne
Frances A
FA
D'Alessio
Ana C
AC
Sharma
Shakti
S
Seckl
Jonathan R
JR
Dymov
Sergiy
S
Szyf
Moshe
M
Meaney
Michael J
MJ
D000107:Acetylation / Q000187:drug effects; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D019175:DNA Methylation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D044127:Epigenesis, Genetic / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation; D006120:Grooming / Q000502:physiology; D006624:Hippocampus / Q000502:physiology; D006655:Histone Deacetylases / Q000187:drug effects; D006657:Histones / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology; D007276:Injections, Intraventricular; D008425:Maternal Behavior / Q000502:physiology*; D008969:Molecular Sequence Data; D010913:Pituitary-Adrenal System / Q000502:physiology; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000502:physiology; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D012097:Repressor Proteins / Q000378:metabolism; D013315:Stress, Psychological
D004791:Enzyme Inhibitors; D006657:Histones; C490623:Nab1 protein, rat; D011965:Receptors, Glucocorticoid; D012097:Repressor Proteins; D006655:Histone Deacetylases