ArticleProceedings of the National Academy of Sciences of the United States of America2009
The role of the dioxin-responsive element cluster between the Cyp1a1 and Cyp1a2 loci in aryl hydrocarbon receptor biology.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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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.
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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
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 96 citations in OpenAlex.
- Sequence variants at CYP1A1-CYP1A2 and AHR associate with coffee consumption.Human molecular genetics · 2011Pooled it
- Habitual coffee consumption poorly correlates with sleep quality and daytime sleepiness: A cross-sectional study.PloS one · 2026Article
- Disruption of the tumor suppressor-like activity of aryl hydrocarbon receptor by arsenic in epithelial cells and human lung cancer.International journal of biological sciences · 2023Article
- Dioxin Disrupts Thyroid Hormone and Glucocorticoid Induction of klf9, a Master Regulator of Frog Metamorphosis.Toxicological sciences : an official journal of the Society of Toxicology · 2022Article
- Species-Specific Differences in Aryl Hydrocarbon Receptor Responses: How and Why?International journal of molecular sciences · 2021Review
- Rodent genetic models of Ah receptor signaling.Drug metabolism reviews · 2021Review
- The Aryl Hydrocarbon Receptor Suppresses Chronic Smoke-Induced Pulmonary Inflammation.Frontiers in toxicology · 2021Article
- Mucus production stimulated by IFN-AhR signaling triggers hypoxia of COVID-19.Cell research · 2020Article
- The Ah Receptor: Adaptive Metabolism, Ligand Diversity, and the Xenokine Model.Chemical research in toxicology · 2020Review
- Dietary Indole-3-Carbinol Activates AhR in the Gut, Alters Th17-Microbe Interactions, and Exacerbates Insulitis in NOD Mice.Frontiers in immunology · 2020Article
- Transcription Factors AhR/ARNT Regulate the Expression ofInternational journal of molecular sciences · 2019Article
- 2,3,7,8‑tetrachlorodibenzo‑p‑dioxin suppresses the growth of human colorectal cancer cells in vitro: Implication of the aryl hydrocarbon receptor signaling.International journal of oncology · 2019Article
- The Aryl Hydrocarbon Receptor and the Maintenance of Lung Health.International journal of molecular sciences · 2018Review
- PBDE-47 and PBDE mixture (DE-71) toxicities and liver transcriptomic changes at PND 22 after in utero/postnatal exposure in the rat.Archives of toxicology · 2018Article
- Isopsoralen Enhanced Osteogenesis by Targeting AhR/ERα.Molecules (Basel, Switzerland) · 2018Article
- 2,3,7,8‑Tetrachlorodibenzo‑p‑dioxin suppresses the growth of human liver cancer HepG2 cells in vitro: Involvement of cell signaling factors.International journal of oncology · 2018Article
- Physiological Regulation of Drug Metabolism and Transport: Pregnancy, Microbiome, Inflammation, Infection, and Fasting.Drug metabolism and disposition: the biological fate of chemicals · 2018Article
- STAT3/p53 pathway activation disrupts IFN-β-induced dormancy in tumor-repopulating cells.The Journal of clinical investigation · 2018Article
- A genome-wide association study in the Japanese population identifies the 12q24 locus for habitual coffee consumption: The J-MICC Study.Scientific reports · 2018Article
- Hyperoxia-mediated transcriptional activation of cytochrome P4501A1 (CYP1A1) and decreased susceptibility to oxygen-mediated lung injury in newborn mice.Biochemical and biophysical research communications · 2018Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The aryl hydrocarbon receptor (AHR) plays a central role in 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin) hepatotoxicity, regulation of xenobiotic metabolism, and hepatovascular development. Each of these processes appears to be dependent on binding of the AHR to dioxin- responsive elements (DREs) within the genome. The Cyp1a1 and Cyp1a2 loci represent linked genes thought to play important roles in AHR biology. In the mouse, 8 DREs are located in the 14-kb intergenic region between the Cyp1a1 and Cyp1a2 genes. Seven of these DREs, collectively known as the DRE cluster (DREC), are located 1.4 kb upstream of the Cyp1a1 transcriptional start site and 12.6 kb upstream of the Cyp1a2 start site. To investigate the role of the DREC in each aspect of AHR biology, we generated a DREC-deficient mouse model through homologous recombination. Using this mouse model, we demonstrate that the DREC controls the adaptive up-regulation of both Cyp1a1 and Cyp1a2 genes in vivo. Using selected aspects of acute hepatic injury as endpoints, we also demonstrate that DREC null mice are more sensitive to dioxin-induced hepatotoxicity than WT mice. The results of parallel toxicologic studies using individual Cyp1a1 and Cyp1a2 null mice support the observation that up-regulation of these P450s is not the cause of many aspects of dioxin hepatotoxicity. Finally, we observed normal closure of the ductus venosus (DV) in DREC null mice. Given the 100% penetrance of patent DV in Ahr null mice, these results indicate that Cyp1a1 and Cyp1a2 do not play a dominant role in AHR-mediated vascular development.
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