HUMAN STEROL CARRIER PROTEIN-X STEROL CARRIER PROTEIN-2 GENE HAS 2 PROMOTERS

The human sterol carrier protein x (SCPx)/sterol carrier protein 2 (SC P2) gene gives rise to two mRNAs: a 2.8 kb mRNA encoding SCPx, a perox isome-associated thiolase, and a 1.5 kb mRNA encoding SCP2, which is t hought to be an intracellular lipid transfer protein. The SCPx/SCP2 ge ne is highly expressed in organs involved in lipid metabolism, but the relative abundance of SCPx and SCP2 mRNAs varies. Here we report that the two transcripts are produced under the direction of two independe nt promoters. We determined the DNA sequence of 3.4 kb of the proximal promoter governing the transcription of SCPx sequences. The promoter governing the transcription of SCP2 sequences was identified 45 kb dow nstream from the SCPx promoter in intron XI. This promoter initiates t ranscription within exon XII. Both the SCPx and SCP2 promoters lack TA TA boxes and initiate transcription at multiple sites. They share feat ures that are found in the promoters of genes encoding other peroxisom al proteins. The basal activities of the two promoters were tested as fusion gene constructs in selected host cells, including BeWo chorioca rcinoma cells, HepG2 hepatoblastoma cells, murine Y1 adrenocortical tu mor cells, and Balb 3T3 fibroblasts. Cell host-specific patterns of pr omoter activity were observed. In addition, 8-Br-cAMP and phorbol myri state acetate were found to increase SCPx promoter activity in a host cell-specific manner. The SCP2 promoter was not significantly influenc ed by these agents. Our findings reveal the basis for the generation o f the two transcripts from the human SCPx/SCP2 gene, document the inde pendent activities of the SCPx and SCP2 promoters, and demonstrate tha t the activities of these promoters are influenced by the host cell.