Constitutive androstane receptor-responsive elements for mouse Cyp1a2 transcriptional activation induced by constitutive androstane receptor ligands. 2023

Yuki Kawasaki, and Nobuo Nemoto, and Tsutomu Sakuma
Department of Toxicology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan; Department of Cancer Cell Biology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan; Laboratory of Public Health, Faculty of Pharmacy, Takasaki University of Health and Welfare, 60 Nakaorui-machi, Takasaki, Gunma, 370-0033, Japan. Electronic address: kawasaki-y@takasaki-u.ac.jp.

The mouse cytochrome P450 1A2 (Cyp1a2) gene is one of the constitutive androstane receptor (CAR, NR1I3) activator-inducible genes, and the regions involved in induction were examined herein. A reporter gene assay indicated the involvement of the -0.2-kb region in the induction of transcriptional activation by the mouse CAR agonist ligand 1,4-bis-[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP). Some putative nuclear receptor-binding elements were identified in this region, and mutations in the elements located at -160/-155 or -153/-148 abolished this induction. An electrophoretic mobility shift assay demonstrated that a fragment comprised of three elements was capable of binding to the CAR/retinoid X receptor alpha (RXRα) heterodimer. The three elements comprise the two elements indicated above and one located at -146/-141. A chromatin immunoprecipitation assay confirmed CAR binding to the region including these elements in chromatin after treatment with TCPOBOP. These results indicate that mouse Cyp1a2 is the direct target of CAR, and binding of the CAR/RXRα heterodimer to the newly identified region in the promoter may be involved in transcriptional activation. Binding motifs were estimated as ER1 (everted repeat with a spacing of 1 nucleotide, -160/-155 and -153/-148) and ER8 (everted repeat with a spacing of 8 nucleotides, formed with -160/-155 and -146/-141).

UI MeSH Term Description Entries
D008024 Ligands A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed) Ligand
D000090702 Constitutive Androstane Receptor A member of the nuclear receptor superfamily (subfamily 1, group I, member 3 [NR1i3]) involved, along with PREGNANE X RECEPTOR, in regulation of cellular responses to the exogenous and endogenous chemicals such as detoxification of XENOBIOTICS. CAR Nuclear Receptor,CAR Orphan Nuclear Receptor,Constitutive Active Receptor,Constitutive Androstane Receptor beta,Active Receptor, Constitutive,Androstane Receptor, Constitutive,Nuclear Receptor, CAR,Receptor, CAR Nuclear,Receptor, Constitutive Active
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015533 Transcriptional Activation Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes. Gene Activation,Genetic Induction,Transactivation,Induction, Genetic,Trans-Activation, Genetic,Transcription Activation,Activation, Gene,Activation, Transcription,Activation, Transcriptional,Genetic Trans-Activation,Trans Activation, Genetic
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D018160 Receptors, Cytoplasmic and Nuclear Intracellular receptors that can be found in the cytoplasm or in the nucleus. They bind to extracellular signaling molecules that migrate through or are transported across the CELL MEMBRANE. Many members of this class of receptors occur in the cytoplasm and are transported to the CELL NUCLEUS upon ligand-binding where they signal via DNA-binding and transcription regulation. Also included in this category are receptors found on INTRACELLULAR MEMBRANES that act via mechanisms similar to CELL SURFACE RECEPTORS. Cytoplasmic Receptor,Cytoplasmic and Nuclear Receptors,Cytosolic and Nuclear Receptors,Hormone Receptors, Cytoplasmic,Hormone Receptors, Nuclear,Nuclear Hormone Receptor,Nuclear Receptor,Nuclear and Cytoplasmic Receptors,Cytoplasmic Hormone Receptors,Cytoplasmic Receptors,Cytosol and Nuclear Receptors,Intracellular Membrane Receptors,Nuclear Hormone Receptors,Nuclear Receptors,Receptors, Cytoplasmic,Receptors, Cytosol and Nuclear,Receptors, Cytosolic and Nuclear,Receptors, Intracellular Membrane,Receptors, Nuclear,Receptors, Nuclear and Cytoplasmic,Hormone Receptor, Nuclear,Membrane Receptors, Intracellular,Receptor, Cytoplasmic,Receptor, Nuclear,Receptor, Nuclear Hormone,Receptors, Cytoplasmic Hormone,Receptors, Nuclear Hormone
D019388 Cytochrome P-450 CYP1A2 A cytochrome P450 enzyme subtype that has specificity for relatively planar heteroaromatic small molecules, such as CAFFEINE and ACETAMINOPHEN. CYP1A2,Phenacetin O-Dealkylase,CYP 1A2,Caffeine Demethylase,Cytochrome P-450 LM(4),Cytochrome P-450 LM4,Cytochrome P-450d,Cytochrome P450 1A2,CYP1A2, Cytochrome P-450,Cytochrome P 450 CYP1A2,Cytochrome P 450 LM4,Cytochrome P 450d,Demethylase, Caffeine,O-Dealkylase, Phenacetin,P-450 LM4, Cytochrome,Phenacetin O Dealkylase

Related Publications

Yuki Kawasaki, and Nobuo Nemoto, and Tsutomu Sakuma
October 2016, Chemical research in toxicology,
Yuki Kawasaki, and Nobuo Nemoto, and Tsutomu Sakuma
August 2017, Journal of applied toxicology : JAT,
Yuki Kawasaki, and Nobuo Nemoto, and Tsutomu Sakuma
October 2002, Biochemical and biophysical research communications,
Yuki Kawasaki, and Nobuo Nemoto, and Tsutomu Sakuma
August 2020, Archives of toxicology,
Yuki Kawasaki, and Nobuo Nemoto, and Tsutomu Sakuma
August 2002, Molecular pharmacology,
Yuki Kawasaki, and Nobuo Nemoto, and Tsutomu Sakuma
December 2020, Molecules (Basel, Switzerland),
Yuki Kawasaki, and Nobuo Nemoto, and Tsutomu Sakuma
January 2019, Toxicological sciences : an official journal of the Society of Toxicology,
Yuki Kawasaki, and Nobuo Nemoto, and Tsutomu Sakuma
December 1988, The Journal of biological chemistry,
Yuki Kawasaki, and Nobuo Nemoto, and Tsutomu Sakuma
July 2013, Toxicology letters,
Copied contents to your clipboard!