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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References
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TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
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Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults. The Adverse Childhood Experiences (ACE) Study
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
TL;DR: For example, this article found a strong relationship between the breadth of exposure to abuse or household dysfunction during childhood and multiple risk factors for several of the leading causes of death in adults.
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How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions.
TL;DR: This review considers recent findings regarding GC action and generates criteria for determining whether a particular GC action permits, stimulates, or suppresses an ongoing stress-response or, as an additional category, is preparative for a subsequent stressor.
Journal ArticleDOI
Protective and Damaging Effects of Stress Mediators
TL;DR: The long-term effect of the physiologic response to stress is reviewed, which I refer to as allostatic load, which is the ability to achieve stability through change.
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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