The human neuronal α1-chimaerin gene contains a position-dependent negative regulatory element in the first exon

Abstract

α1-Chimaerin mRNA, which encodes a neuron-specific GTPase-activating protein for the signal transduction molecule p21 Rac, is highly expressed in certain brain regions and neuronal cell lines. The promoter region of human α1-chimaerin transcriptional unit contains no TATA box, Sp1-binding site or initiator motif. However, a CCAAT box located in the proximal promoter region is essential for promoter activity. We now describe a negative regulatory element in the 5' untranslated region of exon 1 of the human α1-chimaerin gene. Deletion of this 70-bp region from the α1-chimaerin minimal promoter increased the promoter activity 5- to 6-fold. The negative element can suppress heterologous thymidine kinase promoter activity in an orientation- independent manner when placed in its native position. However, its function is position-dependent. The presence of a putative factor in rat liver, HepG2 and SK-N-SH cell nuclear extracts but not in rat brain nuclear extract which interacts with this element suggests a possible role of the negative element in controlling the neuron-specific expression of α1-chimaerin in vivo.