Hepatic transcriptional up-regulator of the rat microsomal epoxide hydrolase gene.
Rat microsomal epoxide hydrolase (mEH) is one of the detoxification enzymes and selectively expressed in liver. A 350-bp DNA fragment of the proximal promoter was found to contain information sufficient to express the mEH gene in hepatoma cells, however not in nonhepatoma cells. We identified two cis-acting elements, epoxide hydrolase proximal element 1 (EHP1) and 2 (EHP2), in this promoter region by using transient transfection assays. Each element is a new cell-type-specific transcriptional up-regulator. The cell-type-specific activity of EHP1 correlates to the limited cell distribution of its cognate transacting factor(s). In the case of EHP2, a similar or possibly the same cognate factor(s) binding to EHP2 was detected by DNase I footprinting and gel retardation assays in both hepatoma and nonhepatoma cells. However, EHP2 functions as an up-regulator only in hepatoma cells. Our finding adds repertoire to a battery of cis-regulatory elements that are required for liver-specific transcription.
Kondo
S
S
Department of Molecular Genetics, Beckman Research Institute of the City of Hope, Duarte, CA 91010.
Gertson
P N
PN
Yokoyama
K
K
Itakura
K
K
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D004851:Epoxide Hydrolases / Q000235:genetics*; D005786:Gene Expression Regulation; D066298:In Vitro Techniques; D008862:Microsomes, Liver / Q000201:enzymology*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D014157:Transcription Factors; D004851:Epoxide Hydrolases