ArticleThe Journal of biological chemistry2015
Response Element Composition Governs Correlations between Binding Site Affinity and Transcription in Glucocorticoid Receptor Feed-forward Loops.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 42 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
- Integrative analysis of mitochondrial and immune pathways in diabetic kidney disease: identification of AASS and CASP3 as key predictors and therapeutic targets.Renal failure · 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
- 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
- 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
- Identification of hippocampal area CA2 in hamster and vole brain.The Journal of comparative neurology · 2024Article
- Identification of hippocampal area CA2 in hamster and vole brain.bioRxiv : the preprint server for biology · 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
- Intimate Relationship Between Stress and Human Alpha‑Herpes Virus 1 (HSV‑1) Reactivation from Latency.Current clinical microbiology reports · 2023Article
- Article
- The power of the (imperfect) palindrome: Sequence-specific roles of palindromic motifs in gene regulation.BioEssays : news and reviews in molecular, cellular and developmental biology · 2022Review
- Muscle mitochondrial remodeling by intermittent glucocorticoid drugs requires an intact circadian clock and muscle PGC1α.Science advances · 2022Article
- Article
- Regulation of Krüppel-Like Factor 15 Expression by Herpes Simplex Virus Type 1 or Bovine Herpesvirus 1 Productive Infection.Viruses · 2021Article
- Glucocorticoid receptor wields chromatin interactions to tune transcription for cytoskeleton stabilization in podocytes.Communications biology · 2021Article
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
Abstract
Combinatorial gene regulation through feed-forward loops (FFLs) can bestow specificity and temporal control to client gene expression; however, characteristics of binding sites that mediate these effects are not established. We previously showed that the glucocorticoid receptor (GR) and KLF15 form coherent FFLs that cooperatively induce targets such as the amino acid-metabolizing enzymes AASS and PRODH and incoherent FFLs exemplified by repression of MT2A by KLF15. Here, we demonstrate that GR and KLF15 physically interact and identify low affinity GR binding sites within glucocorticoid response elements (GREs) for PRODH and AASS that contribute to combinatorial regulation with KLF15. We used deep sequencing and electrophoretic mobility shift assays to derive in vitro GR binding affinities across sequence space. We applied these data to show that AASS GRE activity correlated (r(2) = 0.73) with predicted GR binding affinities across a 50-fold affinity range in transfection assays; however, the slope of the linear relationship more than doubled when KLF15 was expressed. Whereas activity of the MT2A GRE was even more strongly (r(2) = 0.89) correlated with GR binding site affinity, the slope of the linear relationship was sharply reduced by KLF15, consistent with incoherent FFL logic. Thus, GRE architecture and co-regulator expression together determine the functional parameters that relate GR binding site affinity to hormone-induced transcriptional responses. Utilization of specific affinity response functions and GR binding sites by FFLs may contribute to the diversity of gene expression patterns within GR-regulated transcriptomes.
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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.