Cited by 67Epigenetics and DNA MethylationStress Responses and CortisolEstrogen and related hormone effects

The methylated-DNA binding protein MBD2 enhances NGFI-A (egr-1)-mediated transcriptional activation of the glucocorticoid receptor

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Weaver, Ian C. G., Hellstrom, Ian C., Brown, Shelley E., Andrews, Stephen D., Dymov, Sergiy, Diorio, Josie, Zhang, Tie-Yuan, Szyf, Moshe +1 more·2014·Philosophical Transactions of the Royal Society B: Biological Sciences

Abstract

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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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
Published
2014-09-26
Volume
369
Issue
1652
Pages
20130513
ISSN
  • 0962-8436 (ISSN-L)
  • 1471-2970
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
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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