Identification and cross-species comparisons of CYP2F subfamily genes in mammals

Chen, Ning; Whitehead, Sarah E.; Caillat, Alexandre W.; Gavit, Katherine; Isphording, David R.; Kovacevic, David; McCreary, Matthew B.; Hoffman, Susan M.G.

doi:10.1016/s0027-5107(01)00274-3

Cited by 12 publications

(11 citation statements)

References 10 publications

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“…1). In addition, the sequence of CYP2F1 PCR product agreed with the one reported by Chen et al (2002) and Carr et al (2003b) (GenBank accession number NM_000774), with respect to the 12-bp segment in exon 5 that was previously found in a different position (Nhamburo et al, 1990), and the dinucleotide differences at positions 468 and 469 of the CYP2F1 cDNA.…”

Section: Resultssupporting

confidence: 83%

Expression of Cytochrome P450 and Other Biotransformation Genes in Fetal and Adult Human Nasal Mucosa

Zhang¹,

Zhang²,

Liu³

et al. 2005

Drug Metab Dispos

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ABSTRACT:Despite recent progress in the identification and characterization of numerous nasal biotransformation enzymes in laboratory animals, the expression of biotransformation genes in human nasal mucosa remains difficult to study. Given the potential role of nasal biotransformation enzymes in the metabolism of airborne chemicals, including fragrance compounds and therapeutic agents, as well as the potential interspecies differences between laboratory animals and humans, it would be highly desirable to identify those biotransformation genes that are expressed in human nasal mucosa. In this study, a global gene expression analysis was performed to compare biotransformation enzymes expressed in human fetal and adult nasal mucosa to those expressed in liver. The identities of a list of biotransformation genes with apparently nasal mucosa-selective expression were subsequently confirmed by RNA-polymerase chain reaction (PCR) and DNA sequencing of the PCR products. Further quantitative RNA-PCR experiments indicated that, in the fetus, aldehyde dehydrogenase 6 (ALDH6), CYP1B1, CYP2F1, CYP4B1, and UDP glucuronosyltransferase 2A1 are expressed preferentially in the nasal mucosa and that ALDH7, flavin-containing monooxygenase 1, and glutathione S-transferase P1 are at least as abundant in the nasal mucosa as in the liver. The nasal mucosal expression of CYP2E1 was also detected. These findings provide a basis for further explorations of the metabolic capacity of the human nasal mucosa for xenobiotic compounds.

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Section: Resultssupporting

confidence: 83%

Expression of Cytochrome P450 and Other Biotransformation Genes in Fetal and Adult Human Nasal Mucosa

Zhang¹,

Zhang²,

Liu³

et al. 2005

Drug Metab Dispos

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“…The CYP2F1 gene structure, which contains 10 exons and 9 introns, is unique from all genes of the CYP2 family, which have been shown to contain 9 exons and 8 introns (31). The structure described here recognizes an additional 5Ј-untranslated (UTR), exon 1, separated from exon 2 by 1685 bp, which was missing from the CYP2F1 gene structures reported earlier (3,32). Earlier reports concluded that CYP2F1 contained nine exons, but the results presented here demonstrate that the previously reported exon 1 is actually composed of exons 1 and 2, separated by a 1685-bp intron.…”

Section: Cloning and Nucleotide Sequence Of The Human Cyp2f1mentioning

confidence: 44%

Characterization of the Human Lung CYP2F1 Gene and Identification of a Novel Lung-specific Binding Motif

Carr

Wan

Hines

et al. 2003

Journal of Biological Chemistry

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The CYP2F1 gene encodes a cytochrome P450 enzyme capable of bioactivating a number of pulmonary-selective toxicants. The expression of CYP2F1 is highly tissue-selective; the highest expression is observed in the lung with little or no hepatic expression. The objective of these studies was to elucidate the mechanisms that govern the unique tissue-specific regulation of CYP2F1. Cosmid and bacterial artificial chromosome clones were screened and sequenced to identify a gene that spanned 14 kbp containing 10 exons, including an untranslated exon 1. Primer extension analysis and 5 -rapid amplification of cDNA ends were used to identify the transcription start site. Several sequences homologous to known cis-elements were identified in the 5 -upstream region of the CYP2F1 promoter. Transient transfection studies with luciferase reporter constructs demonstrated a significant functional lung cell-specific CYP2F1 promoter region (from position ؊129 to ؉115). DNase footprinting analysis of 1.6 kbp of the upstream sequence with nuclear extracts from human lung tissues revealed one strong DNA-protein complex at ؊152 to ؊182. This nuclear protein (called lung-specific factor, LSF) was present only in lung but not liver or heart tissues. Competitive electrophoretic mobility shift assays characterized a DNA consensus site, within the LSF-binding domain, that was highly similar to two E box motifs, but no known "E box" trans-factors were identified. These studies identified a novel LSF and its consensus sequence that may control tissue-specific expression of CYP2F1.

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“…Defining orthologs between mouse and human also facilitates the creation of appropriate knockout animals. It is often difficult or impossible to identify orthologs of CYP genes in all but very closely related species (Nelson et al 1993), but when sequence similarity, physical location, and protein function all match, this can be done at least tentatively (Chen et al 2002;Hoffman et al 2001). In the case of the CYP2A-T clusters, some orthologous relationships can be reasonably deduced.…”

Section: Discussionmentioning

confidence: 99%

“…The mouse Cyp2a5 locus may be a true ortholog of the human CYP2A6, as they have the most similar sequences (Table 2) and they are located at similar positions within the two clusters (Figure 2A). The single mouse 2f2 and the functional human 2F1 both express proteins with similar substrate ranges and the same limited tissue distribution and are thus considered orthologous (Chen et al 2002). The mRNAs known from the single mouse 2s1 and human 2S1 genes are 81% identical, and these genes are similarly located on the AXL ends of their respective clusters, so they can also be considered orthologous (Hoffman et al 2001).…”

Section: Discussionmentioning

confidence: 99%

“…There is only a single member of the 2f subfamily in the mouse, the functional 2f2 gene, which is located centromeric of and close to the 2t4 gene (Figure 1) in a position exactly corresponding to that of the human 2F1P locus. Unlike the human and gorilla (Chen et al 2002), the mouse does not have a second 2f locus. This was established by the failure of intron 1 and exon 9 primers to amplify from any of the BAC clones and by the lack of hybridization to the Southern blots using a 2f2 exon 9 probe.…”

Section: Modern Humanmentioning

confidence: 99%

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Organization and evolution of the Cyp2 gene cluster on mouse chromosome 7, and comparison with the syntenic human cluster.

Wang

Donley

Keeney

et al. 2003

Environ Health Perspect

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Genes from the cytochrome P450 (CYP) superfamily encode a diverse group of monooxygenases that play important roles in both endogenous processes and in the metabolism of exogenous compounds, including most drugs. A cluster of Cyp2 genes on mouse chromosome 7 was mapped and analyzed in detail and compared with the homologous cluster on human chromosome 19. The mouse cluster includes 22 loci from the same six CYP2 subfamilies-Cyp2a, Cyp2b, Cyp2f, Cyp2g, Cyp2s, Cyp2t-that are found in the human cluster. Twelve of these loci are functional genes, and 10 are pseudogenes. Parts of the mouse and human gene clusters are similarly arranged, but the data indicate that a significantly different series of duplication events created the modern gene organizations in the two species. The comparison of the mouse and human clusters provides new insights into the evolution of gene families, whereas the detailed analysis provides background information that should be informative for future studies on the expression, regulation, and function of specific mouse Cyp2 genes.

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Identification and cross-species comparisons of CYP2F subfamily genes in mammals

Cited by 12 publications

References 10 publications

Expression of Cytochrome P450 and Other Biotransformation Genes in Fetal and Adult Human Nasal Mucosa

Expression of Cytochrome P450 and Other Biotransformation Genes in Fetal and Adult Human Nasal Mucosa

Characterization of the Human Lung CYP2F1 Gene and Identification of a Novel Lung-specific Binding Motif

Organization and evolution of the Cyp2 gene cluster on mouse chromosome 7, and comparison with the syntenic human cluster.

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