Isolation and characterization of the human secretogranin II gene promoter

The goal of this study was to isolate and functionally characterize the hum an secretogranin II (SgII) gene promotor. SgII is a member of the granin fa mily of proteins which are selectively expressed in neurosecretory cells. T he human SgII: promoter contains a consensus TATA box and cyclic AMP respon se element (CRE) 35 and 74 bp upstream of the transcription start site, res pectively, elements also found in the mouse and rat SgII gene promoters. Tr ansfection studies showed that 869 bp of the human SgII promoter were suffi cient to confer cell type-specific expression of an SgII promoter-luciferas e reporter gene in neurosecretory PC-12, GH and BE(2)-M17 cells. The activi ty of the human SgII promoter was also compared in three N-type, human neur oblastoma cell lines [BE(2)-M17, SMS-KAN and SH-SY5Y], which differ markedl y in the level of SgII expression. SgII promoter activities in the neurobla stoma cell lines correlated not only with the levels of SgII but also the l evels of the cyclic AMP response element-binding protein CREB which were hi ghest in BE(2)-M17 cells and lowest in SH-SY5Y cells. To establish that the activity of the human SgII promoter in these neuroblastoma cell lines is d ependent on the level of CREB, rat CREB was overexpressed in SH-SY5Y cells. SgII promoter activity was up to 8-fold higher in SH-SY5Y cells overexpres sing CREB. These results suggest that SgII expression is a marker for neuro nal differentiation in human neuroblastoma cell lines and is dependent on t he level of CREB expression. (C) 2000 Elsevier Science B.V. All rights rese rved.