ArticleProceedings of the National Academy of Sciences of the United States of America2013
Glucocorticoid receptor represses proinflammatory genes at distinct steps of the transcription cycle.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 67 citations in OpenAlex.
- Effects of topical low-dose preservative-free hydrocortisone on intraocular pressure in patients affected by ocular surface disease with and without glaucoma.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2022Trial
- Selective Glucocorticoid Receptor Modulators (SEGRAMs): Can They Improve the Therapeutic Index of Steroid Therapy?Medical science monitor : international medical journal of experimental and clinical research · 2026Review
- Glucocorticoid Receptor Signaling: Multilevel Organization, Roles in Fetal Development, and Postnatal Outcomes.International journal of molecular sciences · 2026Review
- The role of relaxins in blood cell modulation: interactions with relaxin family peptide receptor 1 (RXFP1) and glucocorticoid receptor (GR).Clinical science (London, England : 1979) · 2025Review
- Medication-Related Impacts on Pediatric Bone Health.Journal of the Pediatric Orthopaedic Society of North America · 2025Review
- DFF-ChIP: a method to detect and quantify complex interactions between RNA polymerase II, transcription factors, and chromatin.Nucleic acids research · 2024Article
- Selective Modulation of the Human Glucocorticoid Receptor Compromises GR Chromatin Occupancy and Recruitment of p300/CBP and the Mediator Complex.Molecular & cellular proteomics : MCP · 2024Article
- Mechanisms and Functions of the RNA Polymerase II General Transcription Machinery during the Transcription Cycle.Biomolecules · 2024Review
- Modulating glucocorticoid receptor actions in physiology and pathology: Insights from coregulators.Pharmacology & therapeutics · 2023Review
- Crosstalk between glucocorticoid and mineralocorticoid receptors boosts glucocorticoid-induced killing of multiple myeloma cells.Cellular and molecular life sciences : CMLS · 2023Article
- Epithelial NELF guards intestinal barrier function to ameliorate colitis by maintaining junctional integrity.Mucosal immunology · 2022Article
- Physiological Convergence and Antagonism Between GR and PPARγ in Inflammation and Metabolism.Advances in experimental medicine and biology · 2022Review
- Exploiting dynamic enhancer landscapes to decode macrophage and microglia phenotypes in health and disease.Molecular cell · 2021Review
- Dexamethasone enhances the lung metastasis of breast cancer via a PI3K-SGK1-CTGF pathway.Oncogene · 2021Article
- Nuclear ADP-ribosylation drives IFNγ-dependent STAT1α enhancer formation in macrophages.Nature communications · 2021Article
- Correcting signal biases and detecting regulatory elements in STARR-seq data.Genome research · 2021Article
- Negative elongation factor regulates muscle progenitor expansion for efficient myofiber repair and stem cell pool repopulation.Developmental cell · 2021Article
- Signaling-to-chromatin pathways in the immune system.Immunological reviews · 2021Review
- GLCCI1 Deficiency Induces Glucocorticoid Resistance via the Competitive Binding of IRF1:GRIP1 and IRF3:GRIP1 in Asthma.Frontiers in medicine · 2021Article
- Negative elongation factor complex enables macrophage inflammatory responses by controlling anti-inflammatory gene expression.Nature communications · 2020Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
Abstract
Widespread anti-inflammatory actions of glucocorticoid hormones are mediated by the glucocorticoid receptor (GR), a ligand-dependent transcription factor of the nuclear receptor superfamily. In conjunction with its corepressor GR-interacting protein-1 (GRIP1), GR tethers to the DNA-bound activator protein-1 and NF-κB and represses transcription of their target proinflammatory cytokine genes. However, these target genes fall into distinct classes depending on the step of the transcription cycle that is rate-limiting for their activation: Some are controlled through RNA polymerase II (PolII) recruitment and initiation, whereas others undergo signal-induced release of paused elongation complexes into productive RNA synthesis. Whether these genes are differentially regulated by GR is unknown. Here we report that, at the initiation-controlled inflammatory genes in primary macrophages, GR inhibited LPS-induced PolII occupancy. In contrast, at the elongation-controlled genes, GR did not affect PolII recruitment or transcription initiation but promoted, in a GRIP1-dependent manner, the accumulation of the pause-inducing negative elongation factor. Consistently, GR-dependent repression of elongation-controlled genes was abolished specifically in negative elongation factor-deficient macrophages. Thus, GR:GRIP1 use distinct mechanisms to repress inflammatory genes at different stages of the transcription cycle.
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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.