ArticleMolecular and cellular biology1999
Circadian expression of the steroid 15 alpha-hydroxylase (Cyp2a4) and coumarin 7-hydroxylase (Cyp2a5) genes in mouse liver is regulated by the PAR leucine zipper transcription factor DBP.
Article in Molecular and cellular biology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 166 citations in OpenAlex.
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- Effect of Chronic Cadmium Exposure on Brain and Liver Transporters and Drug-Metabolizing Enzymes in Male and Female Mice Genetically Predisposed to Alzheimer's Disease.Drug metabolism and disposition: the biological fate of chemicals · 2022Article
- Control of complex behavior by astrocytes and microglia.Neuroscience and biobehavioral reviews · 2022Review
- Fibroblast growth factor receptor 3 in hepatocytes protects from toxin-induced liver injury and fibrosis.iScience · 2021Article
- Gene expression profiles during tissue remodeling following bladder outlet obstruction.Scientific reports · 2021Article
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- Space-time logic of liver gene expression at sub-lobular scale.Nature metabolism · 2021Article
- Role of the CLOCK protein in liver detoxification.British journal of pharmacology · 2019Article
- Seasonal Clock Changes Are Underappreciated Health Risks-Also in IBD?Frontiers in medicine · 2019Article
- GαOncotarget · 2018Article
- Molecular Aspects of Circadian Pharmacology and Relevance for Cancer Chronotherapy.International journal of molecular sciences · 2017Review
- Circadian rhythms of liver physiology and disease: experimental and clinical evidence.Nature reviews. Gastroenterology & hepatology · 2016Review
- Circadian rhythms and addiction: mechanistic insights and future directions.Behavioral neuroscience · 2014Review
- Sex differences in the circadian variation of cytochrome p450 genes and corresponding nuclear receptors in mouse liver.Chronobiology international · 2013Article
- Molecular clocks in pharmacology.Handbook of experimental pharmacology · 2013Review
- Integrating circadian activity and gene expression profiles to predict chronotoxicity of Drosophila suzukii response to insecticides.PloS one · 2013Article
- Circadian regulation of kisspeptin in female reproductive functioning.Advances in experimental medicine and biology · 2013Review
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
To study the molecular mechanisms of circadian gene expression, we have sought to identify genes whose expression in mouse liver is regulated by the transcription factor DBP (albumin D-site-binding protein). This PAR basic leucine zipper protein accumulates according to a robust circadian rhythm in nuclei of hepatocytes and other cell types. Here, we report that the Cyp2a4 gene, encoding the cytochrome P450 steroid 15alpha-hydroxylase, is a novel circadian expression gene. This enzyme catalyzes one of the hydroxylation reactions leading to further metabolism of the sex hormones testosterone and estradiol in the liver. Accumulation of CYP2A4 mRNA in mouse liver displays circadian kinetics indistinguishable from those of the highly related CYP2A5 gene. Proteins encoded by both the Cyp2a4 and Cyp2a5 genes also display daily variation in accumulation, though this is more dramatic for CYP2A4 than for CYP2A5. Biochemical evidence, including in vitro DNase I footprinting on the Cyp2a4 and Cyp2a5 promoters and cotransfection experiments with the human hepatoma cell line HepG2, suggests that the Cyp2a4 and Cyp2a5 genes are indeed regulated by DBP. These conclusions are corroborated by genetic studies, in which the circadian amplitude of CYP2A4 and CYP2A5 mRNAs and protein expression in the liver was significantly impaired in a mutant mouse strain homozygous for a dbp null allele. These experiments strongly suggest that DBP is a major factor controlling circadian expression of the Cyp2a4 and Cyp2a5 genes in the mouse liver.
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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.