Regulatory elements for the tissue-specific expression of the rat serine dehydratase-encoding gene.
L-Serine dehydratase (SDH; EC 4.2.1.13), the key enzyme for serine utilization in the rat, is synthesized primarily in the liver. Cis-acting DNA elements required for liver-specific expression of the SDH gene were identified by two approaches: (1) transient expression assays in primary cultured rat hepatocytes, and in rat fibrosarcoma and normal rat kidney epithelial (NRK-52E) cell lines; and (2) in vitro transcription assays with nuclear extracts prepared from rat liver and spleen. Deletion analyses of the 5' flanking sequences of the gene have defined two functionally different regions: (a) a cell-type-specific promoter located between positions -62 and +10, which is sufficient for liver-specific expression; and (b) a distal promoter region between bp -133 and -63 containing positive cis-acting elements that regulate the promoter activity in a non-tissue-specific fashion. No other cis-acting elements essential for liver-specific expression were found in the region of -134 to 2.1 kb upstream relative to the cap site of SDH.
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McArdle Laboratory for Cancer Research, Department of Oncology and Pathology, Medical School, University of Wisconsin, Madison 53706.
Kanamoto
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Ogawa
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Pitot
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HC
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002478:Cells, Cultured; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D012695:L-Serine Dehydratase / Q000235:genetics* / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D015183:Restriction Mapping; D014158:Transcription, Genetic; D014162:Transfection
D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; D011993:Recombinant Fusion Proteins; D015500:Chloramphenicol O-Acetyltransferase; D012695:L-Serine Dehydratase