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Epigenetic programming by maternal behavior.

Ian C G Weaver·Nadia Cervoni·Frances A Champagne·Ana C D'Alessio·Shakti Sharma·Jonathan R Seckl·Sergiy Dymov·Moshe Szyf·Michael J Meaney
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Abstract

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.

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AcetylationAnimalsBase SequenceBlotting, WesternDNA MethylationEnzyme InhibitorsEpigenesis, GeneticFemaleGene Expression RegulationGroomingHippocampusHistone DeacetylasesHistonesHypothalamo-Hypophyseal SystemInjections, IntraventricularMaternal BehaviorMolecular Sequence DataPituitary-Adrenal SystemPolymerase Chain ReactionPromoter Regions, GeneticRatsReceptors, GlucocorticoidRepressor ProteinsStress, PsychologicalJournal ArticleResearch Support, Non-U.S. Gov't

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Ian C G Weaver, Nadia Cervoni, Frances A Champagne, Ana C D'Alessio, Shakti Sharma, Jonathan R Seckl, Sergiy Dymov, Moshe Szyf, Michael J Meaney. 2004-06-27. Epigenetic programming by maternal behavior.. https://doi.org/10.1038/nn1276

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