ArticleMolecular and cellular biology2013
The glucocorticoid receptor and KLF15 regulate gene expression dynamics and integrate signals through feed-forward circuitry.
Article in Molecular and cellular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 107 citations in OpenAlex.
- Article
- Structural and biochemical insight into allosteric regulation of the human 2-aminoadipic semialdehyde synthase, a bifunctional enzyme involved in lysine catabolism.Research square · 2026Article
- Hepatic Glucocorticoid Receptor Action and Glucose Homeostasis.Endocrine reviews · 2026Review
- Article
- Glucocorticoid receptor epigenetic activity in the heart.Epigenetics · 2025Review
- Mifepristone alone and in combination with scAAV9-SMN1 gene therapy improves disease phenotypes in SmnScientific reports · 2025Article
- Benefits of Steroid Injections into Paraspinous Muscles After Spinal Surgery in a Rat Paraspinal Muscle Retraction Model.International journal of molecular sciences · 2025Article
- Acute HSV-1 Ocular Infection Is Impaired in KLF15 Knockout Mice but Stress-Induced Reactivation from Latency Is Prolonged in Male KLF15 Knockout Mice.Pathogens (Basel, Switzerland) · 2025Article
- Ramping up the Heat: Induction of Systemic and Pulmonary Immune Responses and Metabolic Adaptations in Mice.bioRxiv : the preprint server for biology · 2025Article
- A Multiomic Network Approach to Uncover Disease Modifying Mechanisms of Inborn Errors of Metabolism.Journal of inherited metabolic disease · 2025Article
- Human alpha-herpesvirus 1 (HSV-1) viral replication and reactivation from latency are expedited by the glucocorticoid receptor.Journal of virology · 2025Review
- Enhancer RNA transcription pinpoints functional genetic variants linked to asthma.Nature communications · 2025Article
- Integrative Roles of Pro-Inflammatory Cytokines on Airway Smooth Muscle Structure and Function in Asthma.Immunological reviews · 2025Review
- 3-(4-Hydroxy-3-methoxyphenyl) propionic acid mitigates dexamethasone-induced muscle atrophy by attenuating Atrogin-1 and MuRF-1 expression in mouse C2C12 skeletal myotubes.Journal of clinical biochemistry and nutrition · 2025Article
- A Small Molecule Agonist of Krüppel-Like Factor 15 in Proteinuric Kidney Disease.Journal of the American Society of Nephrology : JASN · 2024Article
- Glucocorticoid chronopharmacology promotes glucose metabolism in heart through a cardiomyocyte-autonomous transactivation program.JCI insight · 2024Article
- Glucocorticoid chrono-pharmacology unveils novel targets for the cardiomyocyte-specific GR-KLF15 axis in cardiac glucose metabolism.bioRxiv : the preprint server for biology · 2024Article
- A cell cycle regulator, E2F2, and glucocorticoid receptor cooperatively transactivate the bovine alphaherpesvirus 1 immediate early transcription unit 1 promoter.Journal of virology · 2024Article
- Specificity protein 1 (Sp1) and glucocorticoid receptor (GR) stimulate bovine alphaherpesvirus 1 (BoHV-1) replication and cooperatively transactivate the immediate early transcription unit 1 promoter.Journal of virology · 2024Article
- The precise function of alphaherpesvirus tegument proteins and their interactions during the viral life cycle.Frontiers in microbiology · 2024Review
19 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
The glucocorticoid receptor (GR) regulates adaptive transcriptional programs that alter metabolism in response to stress. Network properties that allow GR to tune gene expression to match specific physiologic demands are poorly understood. We analyzed the transcriptional consequences of GR activation in murine lungs deficient for KLF15, a transcriptional regulator of amino acid metabolism that is induced by glucocorticoids and fasting. Approximately 7% of glucocorticoid-regulated genes had altered expression in Klf15-knockdown (Klf15(-/-)) mice. KLF15 formed coherent and incoherent feed-forward circuits with GR that correlated with the expression dynamics of the glucocorticoid response. Coherent feed-forward gene regulation by GR and KLF15 was characterized by combinatorial activation of linked GR-KLF15 regulatory elements by both factors and increased GR occupancy, while expression of KLF15 reduced GR occupancy at the incoherent target, MT2A. Serum deprivation, which increased KLF15 expression in a GR-independent manner in vitro, enhanced glucocorticoid-mediated induction of feed-forward targets of GR and KLF15, such as the loci for the amino acid-metabolizing enzymes proline dehydrogenase and alpha-aminoadipic semialdehyde synthase. Our results establish feed-forward architecture as an organizational principle for the GR network and provide a novel mechanism through which GR integrates signals and regulates expression dynamics.
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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.