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Optimized Analysis of DNA Methylation and Gene Expression from Small, Anatomically-defined Areas of the Brain
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Epigenetic programming by maternal behavior

Ian C G Weaver1, Nadia Cervoni, Frances A Champagne

  • 1Douglas Hospital Research Center, 6875 LaSalle Blvd., Montréal, Québec H4H 1R3, Canada.

Nature Neuroscience
|June 29, 2004
PubMed

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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