Nature Neuroscience
7, 847 - 854 (2004)
Published online: 27 June 2004; Corrected online: 27 July 2004 | doi:10.1038/nn1276
Epigenetic programming by maternal behaviorIan C G Weaver1, 2, Nadia Cervoni3, Frances A Champagne1, 2, Ana C D'Alessio3, Shakti Sharma1, Jonathan R Seckl4, Sergiy Dymov3, Moshe Szyf2, 3
& Michael J Meaney1, 21
Douglas Hospital Research Center, 6875 LaSalle Blvd., Montréal, Québec H4H 1R3, Canada. 2
McGill Program for the Study of Behaviour, Genes and Environment, McGill University, 3655 Sir William Osler Promenade, Montréal, Québec H3G 1Y6, Canada. 3
Department of Pharmacology and Therapeutics, McGill University, 3655 Sir William Osler Promenade, Montréal, Québec H3G 1Y6, Canada. 4
Molecular Medicine Centre, Edinburgh University, Western General Hospital, Edinburgh EH4 2XU, UK.
Correspondence should be addressed to Moshe Szyf moshe.szyf@mcgill.ca or Michael J Meaney michael.meaney@mcgill.caHere 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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