ArticleHuman genetics2011
Transcriptional control of the human glucocorticoid receptor: identification and analysis of alternative promoter regions.
Article in Human genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- Epigenetic Pathways in Human Disease: The Impact of DNA Methylation on Stress-Related Pathogenesis and Current Challenges in Biomarker Development.EBioMedicine · 2017Pooled it
- The cardiovascular and hypothalamus-pituitary-adrenal axis response to stress is controlled by glucocorticoid receptor sequence variants and promoter methylation.Clinical epigenetics · 2016Trial
- Perinatal glucocorticoid sensitivity in the preterm newborn: molecular mechanisms, endogenous determinants, and clinical implications.Frontiers in endocrinology · 2025Review
- The Yin and Yang of the oxytocin and stress systems: opposites, yet interdependent and intertwined determinants of lifelong health trajectories.Frontiers in endocrinology · 2024Article
- Glucocorticoid Receptor Gene (Genes · 2023Article
- How can early life adversity still exert an effect decades later? A question of timing, tissues and mechanisms.Frontiers in immunology · 2023Review
- Genetic variability in exon 1 of the glucocorticoid receptor gene NR3C1 is associated with postoperative complications.Molecular medicine reports · 2022Article
- The Pathways between Cortisol-Related Regulation Genes and PTSD Psychotherapy.Healthcare (Basel, Switzerland) · 2020Review
- Altered Expression of Glucocorticoid Receptor and Neuron-Specific Enolase mRNA in Peripheral Blood in First-Episode Schizophrenia and Chronic Schizophrenia.Frontiers in psychiatry · 2020Article
- Region-specific glucocorticoid receptor promoter methylation has both positive and negative prognostic value in patients with estrogen receptor-positive breast cancer.Clinical epigenetics · 2019Article
- Epigenetic and Neurological Impairments Associated with Early Life Exposure to Persistent Organic Pollutants.International journal of genomics · 2019Review
- How Stress Gets Under the Skin: Early Life Adversity and Glucocorticoid Receptor Epigenetic Regulation.Current genomics · 2018Review
- NR3C1 hypermethylation in depressed and bullied adolescents.Translational psychiatry · 2018Article
- Where does transcription start? 5'-RACE adapted to next-generation sequencing.Nucleic acids research · 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
- Integrative analysis of methylome and transcriptome in human blood identifies extensive sex- and immune cell-specific differentially methylated regions.Epigenetics · 2015Article
- Frequent promoter hypermethylation and expression reduction of the glucocorticoid receptor gene in breast tumors.Epigenetics · 2014Article
- Epigenetic modulation of glucocorticoid receptors in posttraumatic stress disorder.Translational psychiatry · 2014Article
- MicroRNAs and Glucocorticoid-Induced Apoptosis in Lymphoid Malignancies.ISRN hematology · 2013Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glucocorticoid receptor levels are thought to be controlled by multiple alternative first exons. Seven of these exons are located in an upstream CpG island. In this study, we investigated the promoter activity of the intronic regions between these exons, and their susceptibility to CpG methylation and sequence variability. The seven promoters were cloned into luciferase reporter genes, and their activity measured in ten cell lines. CpG islands of 221 donors were genotyped and the effects of these SNPs were investigated in a reporter gene assay. We showed that each of the first exons was independently controlled by a unique promoter located directly upstream. Promoter activities were cell type-specific, and varied considerably between cell types. Irrespective of the cell type, in vitro methylation effectively silenced all reporter constructs. Eleven SNPs were observed within the CpG island of 221 donors, and a new promoter-specific haplotype was revealed. Four of the minor alleles reduced the reporter gene activity, with cell type specific effects. This complexity within the CpG island helps to explain the variable, tissue-specific transcriptional control of the GR, and provides insight into the mechanisms underlying tissue specific deregulation of GR levels.
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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.