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5′ Gene structure and transcriptional regulation of the CYP4FI rat liver tumor gene
230
Abstracts /Prostaglandins
& other Lipid Mediators 59 (1999) l-235
5’GENE STRUCTURE AND TRANSCRIPTIONAL REGULATION OF THE CYP4Fl RAT LIVER TUMOR GENE Ying Wu Department of Biochemistry and Molecular Pathology, Northeastern Ohio Universities College of Medicine, 4209 State Route 44, P.O. Box 95, Rootstown, OH 44272
CYP4Fl gene was initially identified by its elevated expression in rat primary and transplantable heptoma cells. It encodes an LTB omega-hydroxylase which metabolizes biologically active LTB and thus plays an important “rolein the control of inflammation, lipid homeostasis, and carcmogenesis. Nearly 4kb 5’flanking region has been sequenced. Several tentative PPAR binding sites and other response elements have been assigned. ATG start codon is present in exon 1. The luciferase reporter construct that contains 9OObpupstream sequence has been made to study the transcriptional regulation. In vitro transfection studies by using McRH7777 rat heptoma cell lines has determined the strength of this promoter is 5 times more than that of SV40 promoter activity. 12-Hydroxylated lauric acid, 9-cis retinoic acid and trans-RA can significantly stimulate the gene. The peroxisomal proliferator, pentadecafhrorooctanoic acid and ciprofibrate enhance CYP4Fl gene expression, while WY 14,643 and clofibrate have biphasic effect. The regulation of this gene by inflammatory agent is presently being studied. These results may facilitate understanding of regulation of inflammation, lipid homeostasis, and the pathogenesis of diseases that are related to CYP4F gene.
Abstracts /Prostaglandins
& other Lipid Mediators 59 (1999) l-235
5’GENE STRUCTURE AND TRANSCRIPTIONAL REGULATION OF THE CYP4Fl RAT LIVER TUMOR GENE Ying Wu Department of Biochemistry and Molecular Pathology, Northeastern Ohio Universities College of Medicine, 4209 State Route 44, P.O. Box 95, Rootstown, OH 44272
CYP4Fl gene was initially identified by its elevated expression in rat primary and transplantable heptoma cells. It encodes an LTB omega-hydroxylase which metabolizes biologically active LTB and thus plays an important “rolein the control of inflammation, lipid homeostasis, and carcmogenesis. Nearly 4kb 5’flanking region has been sequenced. Several tentative PPAR binding sites and other response elements have been assigned. ATG start codon is present in exon 1. The luciferase reporter construct that contains 9OObpupstream sequence has been made to study the transcriptional regulation. In vitro transfection studies by using McRH7777 rat heptoma cell lines has determined the strength of this promoter is 5 times more than that of SV40 promoter activity. 12-Hydroxylated lauric acid, 9-cis retinoic acid and trans-RA can significantly stimulate the gene. The peroxisomal proliferator, pentadecafhrorooctanoic acid and ciprofibrate enhance CYP4Fl gene expression, while WY 14,643 and clofibrate have biphasic effect. The regulation of this gene by inflammatory agent is presently being studied. These results may facilitate understanding of regulation of inflammation, lipid homeostasis, and the pathogenesis of diseases that are related to CYP4F gene.