ArticleNucleic acids research2008
Highly individual methylation patterns of alternative glucocorticoid receptor promoters suggest individualized epigenetic regulatory mechanisms.
Article in Nucleic acids research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 102 citations in OpenAlex.
- The cardiovascular and hypothalamus-pituitary-adrenal axis response to stress is controlled by glucocorticoid receptor sequence variants and promoter methylation.Clinical epigenetics · 2016Trial
- Effects of NR3C1 and COMT Genes on Attention-Deficit/Hyperactivity Disorder and Accompanying Aggressiveness: A Cross-Sectional Study in a Clinical Sample.International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience · 2026Article
- Prenatal Hypoxia-Induced Adverse Reaction to Mild Stress is Associated with Depressive-Like Changes in the Glucocorticoid System of Rats.Neurochemical research · 2023Article
- Article
- Genetic variability in exon 1 of the glucocorticoid receptor gene NR3C1 is associated with postoperative complications.Molecular medicine reports · 2022Article
- Antenatal Steroids and Cord Blood T-cell Glucocorticoid Receptor DNA Methylation and Exon 1 Splicing.Reproductive sciences (Thousand Oaks, Calif.) · 2022Article
- Understanding the Psychological, Physiological, and Genetic Factors Affecting Precision Pain Medicine: A Narrative Review.Journal of pain research · 2021Review
- Selective Activation of AlternativeGenes · 2018Article
- The tobacco carcinogen NNK drives accumulation of DNMT1 at the GR promoter thereby reducing GR expression in untransformed lung fibroblasts.Scientific reports · 2018Article
- Childhood adversity and epigenetic regulation of glucocorticoid signaling genes: Associations in children and adults.Development and psychopathology · 2016Review
- Where does transcription start? 5'-RACE adapted to next-generation sequencing.Nucleic acids research · 2016Article
- Antenatal hypoxia induces epigenetic repression of glucocorticoid receptor and promotes ischemic-sensitive phenotype in the developing heart.Journal of molecular and cellular cardiology · 2016Article
- DNA methylation: conducting the orchestra from exposure to phenotype?Clinical epigenetics · 2016Review
- Endothelial glucocorticoid receptor promoter methylation according to dexamethasone sensitivity.Journal of molecular endocrinology · 2015Article
- Hypermethylation of glucocorticoid receptor gene promoter results in glucocorticoid receptor gene low expression in peripheral blood mononuclear cells of patients with systemic lupus erythematosus.Rheumatology international · 2015Article
- Maternal Deprivation of Lewis Rat Pups Increases the Severity of Experi-mental Periodontitis in Adulthood.The open dentistry journal · 2015Article
- Frequent promoter hypermethylation and expression reduction of the glucocorticoid receptor gene in breast tumors.Epigenetics · 2014Article
- Fetal hypoxia increases vulnerability of hypoxic-ischemic brain injury in neonatal rats: role of glucocorticoid receptors.Neurobiology of disease · 2014Article
- Glucocorticoid receptor gene (NR3C1) methylation following stressful events between birth and adolescence. The TRAILS study.Translational psychiatry · 2014Article
- Differential regulation of glucocorticoid receptor expression in distinct columns of periaqueductal grey in rats with behavioural disability following nerve injury.Cellular and molecular neurobiology · 2013Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.