ArticleNucleic acids research2017
Tethering not required: the glucocorticoid receptor binds directly to activator protein-1 recognition motifs to repress inflammatory genes.
Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
40 citing papers in PubMed.
- Molecular crosstalk between gas transmitters and catecholamine biosynthesis pathways: a narrative review.Medical gas research · 2027Review
- Spatially resolved profiling of steroid nuclear receptors reveals a role for the disordered N-terminal domains in genome targeting and AP-1 interaction.Genome research · 2026Article
- How post-translational modifications impact glucocorticoid receptor function in human pathologies.Cell communication and signaling : CCS · 2026Review
- Glucocorticoid Receptor Signaling: Multilevel Organization, Roles in Fetal Development, and Postnatal Outcomes.International journal of molecular sciences · 2026Review
- Article
- Decreased Glucocorticoid Receptor Expression and Function in Cord Blood Immune Cells from Preterm Neonates with Morbidity.International journal of molecular sciences · 2025Article
- Perinatal glucocorticoid sensitivity in the preterm newborn: molecular mechanisms, endogenous determinants, and clinical implications.Frontiers in endocrinology · 2025Review
- The Subcutaneous Adipose Microenvironment as a Determinant of Body Fat Development in Polycystic Ovary Syndrome.Journal of the Endocrine Society · 2024Article
- The Glucocorticoid Receptor: Isoforms, Functions, and Contribution to Glucocorticoid Sensitivity.Endocrine reviews · 2024Review
- Glucocorticoid receptor action in prostate cancer: the role of transcription factor crosstalk.Frontiers in endocrinology · 2024Review
- High-throughput screening of glucocorticoid-induced enhancer activity reveals mechanisms of stress-related psychiatric disorders.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Treating the Side Effects of Exogenous Glucocorticoids; Can We Separate the Good From the Bad?Endocrine reviews · 2023Review
- Hidden modes of DNA binding by human nuclear receptors.Nature communications · 2023Article
- Review
- Macrophagic AMPKα1 orchestrates regenerative inflammation induced by glucocorticoids.EMBO reports · 2023Article
- Machine learning reveals STAT motifs as predictors for GR-mediated gene repression.Computational and structural biotechnology journal · 2023Article
- The multivalency of the glucocorticoid receptor ligand-binding domain explains its manifold physiological activities.Nucleic acids research · 2022Article
- Discovery of a novel nonsteroidal selective glucocorticoid receptor modulator by virtual screening and bioassays.Acta pharmacologica Sinica · 2022Article
- Glucocorticoid circadian rhythms in immune function.Seminars in immunopathology · 2022Review
- Plasma Proteomics in Healthy Subjects with Differences in Tissue Glucocorticoid Sensitivity Identifies A Novel Proteomic Signature.Biomedicines · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
Abstract
The glucocorticoid receptor (GR) is a ligand-regulated transcription factor that controls the expression of extensive gene networks, driving both up- and down-regulation. GR utilizes multiple DNA-binding-dependent and -independent mechanisms to achieve context-specific transcriptional outcomes. The DNA-binding-independent mechanism involves tethering of GR to the pro-inflammatory transcription factor activator protein-1 (AP-1) through protein-protein interactions. This mechanism has served as the predominant model of GR-mediated transrepression of inflammatory genes. However, ChIP-seq data have consistently shown GR to occupy AP-1 response elements (TREs), even in the absence of AP-1. Therefore, the current model is insufficient to explain GR action at these sites. Here, we show that GR regulates a subset of inflammatory genes in a DNA-binding-dependent manner. Using structural biology and biochemical approaches, we show that GR binds directly to TREs via sequence-specific contacts to a GR-binding sequence (GBS) half-site found embedded within the TRE motif. Furthermore, we show that GR-mediated transrepression observed at TRE sites to be DNA-binding-dependent. This represents a paradigm shift in the field, showing that GR uses multiple mechanisms to suppress inflammatory gene expression. This work further expands our understanding of this complex multifaceted transcription factor.
Indexed as
Identifiers
What OpenQuestion holds
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.