The promoter activity of the phospholipase C-gamma 2 gene is regulated by a cell-type-specific control element

Abstract

We have cloned and characterized a genomic DNA spanning the 5'-flanking region, the first and second exons, and the first intron of the human PLC-gamma 2 gene. The proximal upstream region is highly CC-rich and lacks a TATA box, whereas the distal region contains several AT-rich tracts. Multiple transcription initiation sites were identified by primer extension analysis, Based on the transient transfection assays, the major transcriptional activation element was identified between -183 and +43 (G2SE) and a transcriptional repressive element was found between -303 and -184 (G2RE). The expression of PLC-gamma 2 in various cell lines was examined using monoclonal anti-PLC-gamma 2 antibody, PLC-gamma 2 was highly expressed in B-cell lines such as Daudi, SP2, and Ramos cells, whereas it existed at very low levels in Jurkat, 3T3-L1, NBL-7, and C6Bu-1 cells. Moderate levels of PLC-gamma 2 were also detected in C2C12, P19, U937, HL60, A431, and PC12 cells. The 4-kb genomic fragment upstream of -1,654 was able to activate transcription from the PLC-gamma 2 promoter in Daudi and C2C12 cells, but not in Jurkat cells, which is consistent with the PLC-gamma 2 protein expression levels in those cell lines. These results suggest that the cell-type-specific expression of PLC-gamma 2 might be attributed to the transcriptional regulation by the upstream cis-element.