ArticleMolecular pharmacology2005
Alternative promoters determine tissue-specific expression profiles of the human microsomal epoxide hydrolase gene (EPHX1).
Article in Molecular pharmacology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 28 citations in OpenAlex.
- Article
- Article
- The Multifaceted Role of Epoxide Hydrolases in Human Health and Disease.International journal of molecular sciences · 2020Review
- Microsomal epoxide hydrolase 1 (EPHX1): Gene, structure, function, and role in human disease.Gene · 2015Review
- Intronic DNA elements regulate Nrf2 chemical responsiveness of the human microsomal epoxide hydrolase gene (EPHX1) through a far upstream alternative promoter.Biochimica et biophysica acta · 2014Article
- Article
- Expression of a novel mRNA transcript for human microsomal epoxide hydrolase (EPHX1) is regulated by short open reading frames within its 5'-untranslated region.RNA (New York, N.Y.) · 2013Article
- Differential regulation of the mouse and human Wnt5a alternative promoters A and B.DNA and cell biology · 2012Article
- The expression of human microsomal epoxide hydrolase is predominantly driven by a genetically polymorphic far upstream promoter.The Journal of pharmacology and experimental therapeutics · 2009Article
- Article
- Variability in human sensitivity to 1,3-butadiene: influence of polymorphisms in the 5'-flanking region of the microsomal epoxide hydrolase gene (EPHX1).Toxicological sciences : an official journal of the Society of Toxicology · 2005Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Microsomal epoxide hydrolase (EPHX1) catalyzes hydration reactions that determine the cellular disposition of reactive epoxide derivatives. Whereas the previously defined EPHX1 exon 1 sequence (E1) is derived from a promoter proximal to exon 2 of the EPHX1 coding region, in this investigation, we identified an alternative EPHX1 exon 1 sequence, E1-b, originating from a gene promoter localized approximately 18.5 kb upstream of exon 2. Northern hybridizations demonstrated that the E1-b variant is widely expressed and that the E1-b promoter functions as the primary driver of EPHX1 expression in human tissues. In contrast, the E1 promoter directs expression only in the liver. To examine the basis for liver-specific usage of the E1 promoter, we identified several potential cis-regulatory elements that included GATA (-110/-105) and hepatocyte nuclear factor 3 (HNF3) (-96/-88) motifs. GATA-4 was the principal GATA family member interacting with its respective motif, whereas both HNF3alpha and HNF3beta were capable of interacting with the HNF3 element. GATA-4 and HNF3alpha/HNF3beta DNA binding complexes were enriched in hepatic cells. Site-directed mutagenesis and transactivation analyses of the E1 promoter revealed that GATA-4 is probably a principal factor that regulates liver-specific expression of the E1 variant, with HNF3alpha and HNF3beta acting to negatively regulate GATA-4 function in hepatic cells.
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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.