Environmental programming of stress responses through DNA methylation: life at the interface between a dynamic environment and a fixed genome.
Michael J. Meaney,Moshe Szyf +1 more
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TLDR
It is demonstrated that the structural modifications of the DNA can be established through environmental programming and that, in spite of the inherent stability of this epigenomic marker, it is dynamic and potentially reversible.Abstract:
Early experience permanently alters behavior and physiology. These effects are, in part, mediated by sustained alterations in gene expression in selected brain regions. The critical question concerns the mechanism of these environmental “programming” effects. We examine this issue with an animal model that studies the consequences of variations in mother-infant interactions on the development of individual differences in behavioral and endocrine responses to stress in adulthood. Increased levels of pup licking/grooming by rat mothers in the first week of life alter DNA structure at a glucocorticoid receptor gene promoter in the hippocampus of the offspring. Differences in the DNA methylation pattern between the offspring of high- and low-lickinglgrooming mothers emerge over the first week of life; they are reversed with cross-fostering; they persist into adulthood; and they are associated with altered histone acetylation and transcription factor (nerve growth factor-induced clone A [NGFIA]) binding to the glucocorticoid receptor promoter. DNA methylation alters glucocorticoid receptor expression through modifications of chromatin structure. Pharmacological reversal of the effects on chromatin structure completely eliminates the effects of maternal care on glucocorticoid receptor expression and hypothalamic-pituitary-adrenal (HPA) responses to stress, thus suggesting a causal relation between the maternally induced, epigenetic modification of the glucocorticoid receptor gene and the effects on stress responses in the offspring. These findings demonstrate that the structural modifications of the DNA can be established through environmental programming and that, in spite of the inherent stability of this epigenomic marker, it is dynamic and potentially reversible.read more
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Deubiquitinating Enzyme OTU5 Contributes to DNA Methylation Patterns and Is Critical for Phosphate Nutrition Signals.
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TL;DR: Across both cultures, psychological control was significantly associated with increased cortisol levels as indexed by AUCg, and mediation analyses demonstrated that psychological control fully explained cultural differences in children's cortisol stress response.
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Vincent J. Felitti,Robert F. Anda,Dale F. Nordenberg,David F. Williamson,Alison M. Spitz,Valerie J. Edwards,Mary P. Koss,James S. Marks +7 more
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Journal ArticleDOI
How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions.
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Journal ArticleDOI
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Journal ArticleDOI
Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex
Xinsheng Nan,Huck-Hui Ng,Colin A. Johnson,Carol D. Laherty,Bryan M. Turner,Robert N. Eisenman,Adrian Bird +6 more
TL;DR: The data suggest that two global mechanisms of gene regulation, DNA methylation and histone deacetylation, can be linked by MeCP2, an abundant nuclear protein that is essential for mouse embryogenesis.
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