The methylated-DNA binding protein MBD2 enhances NGFI-A (egr-1)-mediated transcriptional activation of the glucocorticoid receptor
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Variations in maternal care in the rat influence the epigenetic state and transcriptional activity of glucocorticoid receptor (GR) gene in the hippocampus. The mechanisms underlying this maternal effect remained to be defined, including the nature of the relevant maternally regulated intracellular signalling pathways. We show here that increased maternal licking/grooming (LG), which stably enhances hippocampal GR expression, paradoxically increases hippocampal expression of the methyl-CpG binding domain protein-2 (MBD2) and MBD2 binding to the exon 1 7 GR promoter. Knockdown experiments of MBD2 in hippocampal primary cell culture show that MBD2 is required for activation of exon 1 7 GR promoter. Ectopic co-expression of nerve growth factor-inducible protein A (NGFI-A) with MBD2 in HEK 293 cells with site-directed mutagenesis of the NGFI-A response element within the methylated exon 1 7 GR promoter supports the hypothesis that MBD2 collaborates with NGFI-A in binding and activation of this promoter. These data suggest a possible mechanism linking signalling pathways, which are activated by behavioural stimuli and activation of target genes.
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Szyf, M. (2021) · Elsevier eBooks · doi:10.1016/b978-0-323-90752-1.00001-8 · Cited by 1 · see citing works
Olson, D. (2020) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.733993761.793578528
DNA Methylation as an Epigenetic Mechanism of Anticipation
Moshe Szyf, A. (2022) · Cognitive systems monographs · doi:10.1007/978-3-031-17678-4_2
Epigenetic Processes as Mediators of the Impact of the Social Environment
Moshe Szyf, A. (2024) · Springer eBooks · doi:10.1007/978-3-031-59286-7_6
Epigenetic mechanisms in stress and the hypothalamic-pituitary-adrenal axis
WEAVER, I. C. G. (2026) · Handbook of clinical neurology · doi:10.1016/b978-0-443-19043-8.00018-9
Self-citationAnimal models with construct validity for studying epigenetic processes in neurobehavior
LAX, E., BERHE, M., & Yadid, G. (2026) · Handbook of clinical neurology · doi:10.1016/b978-0-443-19043-8.00028-1
Epigenetic architecture of the developing brain
Moshe Szyf, A. (2026) · Handbook of clinical neurology · doi:10.1016/b978-0-443-19043-8.00022-0
- Authors
- Weaver, I. C. G., Hellstrom, I. C., Brown, S. E., Andrews, S. D., Dymov, S., Diorio, J., Zhang, T.-Y., Szyf, M., & Meaney, M. J.
- Affiliations
- Dalhousie University (CA)
- Douglas Mental Health University Institute (CA)
- McGill University (CA)
- Lumder Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, 6875 LaSalle Boulevard, Montréal, Québec, Canada H4H 1R3
- Sackler Program for Epigenetics and Psychobiology at McGill University, Montréal, Québec, Canada H3A 0G4
- Corresponding author
- Meaney, Michael J.
- Venue
- Philosophical Transactions of the Royal Society B: Biological Sciences
- Publisher
- The Royal Society
- Published
- 2014-09-26
- Volume
- 369
- Issue
- 1652
- Pages
- 20130513
- ISSN
- 0962-8436 (ISSN-L)
- 1471-2970
- PMC
- PMC4142034
- OpenAlex
- W2000065206
- Cited by
- 67
- References
- 44
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 2 · 2023: 5 · 2022: 2 · 2021: 6 · 2020: 5 · 2019: 6 · 2018: 9 · 2017: 12 · 2016: 6 · 2015: 6 · 2014: 3
- FWCI
- 3.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Philosophical Transactions of the Royal Society B Biological Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- MBD2, NGFI-A, EGR1, glucocorticoid receptor, transcriptional activation, DNA methylation, hippocampus, maternal care, epigenetics
- MeSH terms
- Animals, DNA-Binding Proteins, Hippocampus, Humans, Maternal Behavior, Receptors, Glucocorticoid, Blotting, Western, Signal Transduction, Transcriptional Activation, Mutagenesis, Site-Directed, In Situ Hybridization, DNA Primers, Rats, Long-Evans, Chromatin Immunoprecipitation, Rats, Early Growth Response Protein 1, Gene Knockdown Techniques, HEK293 Cells, Real-Time Polymerase Chain Reaction
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