Maternal programming of steroid receptor expression and phenotype through DNA methylation in the rat
Abstract
Increased levels of pup licking/grooming and arched-back nursing by rat mothers over the first week of life alter the epigenome 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 licking/grooming--arched-back mothers emerge over the first week of life, are reversed with cross-fostering, persist into adulthood and are associated with altered histone acetylation and transcription factor (NGFI-A) binding to the glucocorticoid receptor promoter. Central infusion of the adult offspring with the histone deacetylase inhibitor trichostatin A removes the previously defined epigenomic group differences in histone acetylation, DNA methylation, NGFI-A binding, glucocorticoid receptor expression, and hypothalamic-pituitary-adrenal responses to stress, thus suggesting a causal relation between the epigenomic state, glucocorticoid receptor expression and the effects of maternal care on stress responses in the offspring. These findings demonstrate that an epigenomic state of a gene can be established through a behavioral mode of programming and that in spite of the inherent stability of this epigenomic mark, it is dynamic and potentially reversible.
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The absence of early nurturing maternal behavior in rodents leads to increased methylation of exon 17, a NGFI-A regulated promoter of the GR NR3C1 gene.
“The absence of early nurturing maternal behavior in rodents leads to increased methylation, a covalent modification involved in epigenetic regulation of DNA, of exon 17, a NGFI-A regulated promoter of the GR NR3C1 gene (Meaney & Szyf, 2005; Szyf, Weaver, Champagne, Diorio, & Meaney, 2005).”
From Associations Between Early Life Stress and Gene Methylation in Children (2015) · cites this paper as Szyf et al., 2005
Increased CpG methylation within the glucocorticoid receptor promoter is associated with a sluggish HPA stress response and is associated with poor maternal care in rodents and early life abuse in human suicide victims.
“Likewise the increased CpG methylation within the GR promotor is associated with a sluggish HPA stress response and is associated with poor maternal care in rodents and early life abuse in human suicide victims.”
From Neurobiological and Systemic Effects of Chronic Stress (2017) · cites this paper as [32]
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- Authors
- Szyf, M., Weaver, I. C. G., Champagne, F. A., Diorio, J., & Meaney, M. J.
- Affiliations
- Douglas Mental Health University Institute (CA)
- Corresponding author
- Meaney, Michael J.
- Venue
- Frontiers in Neuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2005-10
- Volume
- 26
- Issue
- 3-4
- Pages
- 139-162
- ISSN
- 0091-3022 (ISSN-L)
- OpenAlex
- W2146840535
- Cited by
- 348
- References
- 249
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 7 · 2023: 7 · 2022: 8 · 2021: 11 · 2020: 11 · 2019: 10 · 2018: 18 · 2017: 14 · 2016: 21 · 2015: 27 · 2014: 17 · 2013: 27 · 2012: 27
- FWCI
- 1.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Frontiers in Neuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Keywords
- maternal programming, DNA methylation, glucocorticoid receptor, hippocampus, epigenetic inheritance, histone acetylation, NGFI-A, trichostatin A, stress response, cross-fostering
- MeSH terms
- Animals, Corticotropin-Releasing Hormone, Female, Gene Expression Regulation, Grooming, Hippocampus, Interpersonal Relations, Male, Maternal Behavior, Phenotype, Promoter Regions, Genetic, Receptors, Glucocorticoid, Stress, Psychological, DNA Methylation, Epigenesis, Genetic, Rats
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