Maternal care associated with methylation of the estrogen receptor-alpha1b promoter and estrogen receptor-alpha expression in the medial preoptic area of female offspring.
Variations in maternal behavior are associated with differences in estrogen receptor (ER)-alpha expression in the medial preoptic area (MPOA) and are transmitted across generations such that, as adults, the female offspring of mothers that exhibit increased pup licking/grooming (LG) over the first week postpartum (i.e. high LG mothers) show increased ERalpha expression in the MPOA and are themselves high LG mothers. In the present studies, cross-fostering confirmed an association between maternal care and ERalpha expression in the MPOA; the biological offspring of low LG mothers fostered at birth to high LG dams show increased ERalpha expression in the MPOA. Cross-fostering the biological offspring of high LG mothers to low LG dams produces the opposite effect. We examined whether the maternal programing of ERalpha expression is associated with differences in methylation of the relevant ERalpha promoter. Levels of cytosine methylation across the ERalpha1b promoter were significantly elevated in the adult offspring of low, compared with high, LG mothers. Differentially methylated regions included a signal transducer and activator of transcription (Stat)5 binding site and the results of chromatin immunoprecipitation assays revealed decreased Stat5b binding to the ERalpha1b promoter in the adult offspring of low, compared with high, LG mothers. Finally, we found increased Stat5b levels in the MPOA of neonates reared by high, compared with low, LG mothers. These findings suggest that maternal care is associated with cytosine methylation of the ERalpha1b promoter, providing a potential mechanism for the programming of individual differences in ERalpha expression and maternal behavior in the female offspring.
Champagne
Frances A
FA
Douglas Hospital Research Center, Montréal, Québec, Canada H4H 1R3.
Weaver
Ian C G
IC
Diorio
Josie
J
Dymov
Sergiy
S
Szyf
Moshe
M
Meaney
Michael J
MJ
D000818:Animals; D019175:DNA Methylation; D051766:Early Growth Response Protein 1 / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D047468:Immunoprecipitation; D008425:Maternal Behavior; D011247:Pregnancy; D011301:Preoptic Area / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D051381:Rats; D020318:Rats, Long-Evans; D050799:STAT5 Transcription Factor / Q000032:analysis / Q000378:metabolism
D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D047628:Estrogen Receptor alpha; D050799:STAT5 Transcription Factor; C494097:Stat5b protein, rat