A negative regulatory element in the rat dopamine beta-hydroxylase gene contributes to the cell type specificity of expression.
Dopamine beta-hydroxylase (DBH) catalyzes the synthesis of the neurohormone norepinephrine and is expressed only in noradrenergic and adrenergic cells of the nervous and endocrine systems. We have previously described a positive-acting genetic regulatory element of the DBH that contributes to the restricted expression of this gene. In the study described here, we identify and characterize a negative-acting regulatory element within the 5'-flanking region of the rat DBH gene. This negative regulatory element, which is located between -282 and -232, represses transcription from the DBH promoter in cell lines of noncatecholaminergic origin and binds to nuclear factors found in extracts from both the catecholaminergic cell line SHSY-5Y and the noncatecholaminergic cell lines JEG-3 and C6. The negative regulatory region will reduce transcription from a heterologous promoter in two noncatecholaminergic cell lines. These experiments demonstrate that the selective expression of the DBH gene is controlled by both positive- and negative-acting genetic regulatory elements.
Shaskus
J
J
Department of Biochemistry and Molecular Biology, Oregon Health Sciences University, Portland 97201.
Zellmer
E
E
Lewis
E J
EJ
D000818:Animals; D001483:Base Sequence; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D004299:Dopamine beta-Hydroxylase / Q000032:analysis / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D005809:Genes, Regulator / Q000235:genetics*; D005910:Glioma / Q000737:chemistry / Q000201:enzymology / Q000473:pathology; D006801:Humans; D008969:Molecular Sequence Data; D009447:Neuroblastoma / Q000737:chemistry / Q000201:enzymology / Q000473:pathology; D011401:Promoter Regions, Genetic; D051381:Rats; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D014157:Transcription Factors; D004299:Dopamine beta-Hydroxylase