The DOI matches its Crossref record; 56 of the 56 references it cites were found in a registry or an index.
Highly individual methylation patterns of alternative glucocorticoid receptor promoters suggest individualized epigenetic regulatory mechanisms
Open accessAbstract
The transcription start sites (TSS) and promoters of many genes are located in upstream CpG islands. Methylation within such islands is known for both imprinted and oncogenes, although poorly studied for other genes, especially those with complex CpG islands containing multiple first exons and promoters. The glucocorticoid receptor (GR) CpG island contains seven alternative first exons and their promoters. Here we show for the five GR promoters activated in PBMCs that methylation patterns are highly variable between individuals. The majority of positions were methylated at levels >25% in at least one donor affecting each promoter and TSS. We also examined the evolutionarily conserved transcription factor binding sites (TFBS) using an improved in silico phylogenetic footprinting technique. The majority of these contain methylatable CpG sites, suggesting that methylation may orchestrates alternative first exon usage, silencing and controlling tissue-specific expression. The heterogeneity observed may reflect epigenetic mechanisms of GR fine tuning, programmed by early life environment and events. With 78% of evolutionarily conserved alternative first exons falling into such complex CpG islands, their internal structure and epigenetic modifications are bound to be biologically important, and may be a common transcriptional control mechanism used throughout many phyla.
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“The results of these studies consistently demonstrated that stress or trauma was correlated with higher methylation of exon 1F of NR3C1, which is the homolog of exon 17 in the rat (Turner, Pelascini, Macedo, & Muller, 2008).”
From Associations Between Early Life Stress and Gene Methylation in Children (2015) · cites this paper as Turner et al., 2008
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Epigenetic differences arise during the lifetime of monozygotic twins
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International Journal of Molecular Medicine
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- McCormick, 2000, Molecular Endocrinology, 14, 506, 10.1210/me.14.4.506 · DOI
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Labonte, B., Yerko, V., Gross, J., Mechawar, N., Meaney, M. J., Szyf, M., & Turecki, G. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.01.034 · Cited by 345
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Associations Between Early Life Stress and Gene Methylation in Children
Romens, S. E., McDonald, J., Svaren, J., & Pollak, S. D. (2015) · Child Development · doi:10.1111/cdev.12270 · Cited by 299
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DNA methylation: conducting the orchestra from exposure to phenotype?
Leenen, F. A. D., Muller, C. P., & Turner, J. D. (2016) · Clinical Epigenetics · doi:10.1186/s13148-016-0256-8 · Cited by 200
Metadata
- Authors
- Turner, J. D., Pelascini, L. P. L., Macedo, J. A., & Muller, C. P.
- Affiliations
- Laboratoire National de Santé (LU)
- Corresponding author
- Muller, C. P.
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-11-12
- Volume
- 36
- Issue
- 22
- Pages
- 7207-7218
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC2602793
- OpenAlex
- W2169090691
- Cited by
- 104
- References
- 56
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 5 · 2021: 2 · 2020: 2 · 2018: 6 · 2017: 2 · 2016: 5 · 2015: 12 · 2014: 13 · 2013: 10 · 2012: 19
- FWCI
- 3.29
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nucleic Acids Research (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (GRK 1389/1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
- Keywords
- glucocorticoid receptor, alternative first exons, promoter methylation, CpG islands, transcription start sites, transcription factor binding sites, phylogenetic footprinting, tissue-specific gene expression, epigenetic regulation, peripheral blood mononuclear cells
- MeSH terms
- Adult, Aged, Animals, Binding Sites, Cattle, Female, Humans, Male, Middle Aged, Phylogeny, Promoter Regions, Genetic, Receptors, Glucocorticoid, Transcription Factors, CpG Islands, DNA Methylation, Genomics, Transcription Initiation Site, Epigenesis, Genetic, Mice, Rats
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