A negative regulatory element in the rat dopamine beta-hydroxylase gene contributes to the cell type specificity of expression.

Abstract

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.