Endocrinology, Vol 137, 3815-3822, Copyright © 1996 by Endocrine Society

ARTICLES

Cell-specific expression of the rat secretogranin II promoter

LC Jones, RN Day, SJ Pittler, DL Valentine and JG Scammell
Department of Pharmacology, University of South Alabama, Mobile 36688, USA.

Secretogranin II (SgII) is a member of the granin family of secretory proteins, which are selectively expressed in neuroendocrine cells. As a first step in understanding the molecular basis for cell type-specific expression of SgII, we isolated a 12-kb clone from a rat genomic library that contained the entire rat SgII coding region, the transcription initiation site, and approximately 3 kb of 5'-flanking region. Within 75 bp of the transcription start site (+1) we located a TATA box and a consensus cAMP responsive element. Within the 5'- flanking region, a number of potential cis-acting elements were identified, including 2 Pit-1 binding sites, 15 E box motifs, and near- perfect matches for AP-1 and AP-2 sites. To demonstrate cell type- specific expression the rat SgII gene, a plasmid containing 2.6 kb of the 5'-flanking region of the SgII gene fused to the luciferase reporter gene (p2774Luc) was transfected into rat pheochromocytoma PC- 12 cells, rat pituitary GH4C1 (GH) cells, human BE(2)-M17 (M17) neuroblastoma cells, and mouse fibroblast NIH/3T3 cells. The promoter activity was 6- to 36-fold higher in neuroendocrine cells than in NIH/ 3T3 cells. Progressive deletions in the 5'-flanking region to 61 bp upstream of the start site (p223Luc) had no effect on promoter activity in PC-12 cells. On the other hand, a 5'-deletion in the SgII promoter to -1032 increased promoter activity 3.8-fold in GH cells. This level of expression was maintained when the SgII promoter was further truncated to -189, whereas truncation to -61 resulted in a 2.6-fold reduction in promoter activity. These results suggest that the sequence between -61 and +162 bp is sufficient for SgII promoter activity in PC- 12 cells. However, other elements in the 5'-flanking region contribute to both positive and negative regulation of the rat SgII gene in GH cells.

This article has been cited by other articles:

				J. Xie and M. S. Roberson 3', 5'-Cyclic Adenosine 5'-Monophosphate Response Element-Dependent Transcriptional Regulation of the Secretogranin II Gene Promoter Depends on Gonadotropin-Releasing Hormone-Induced Mitogen-Activated Protein Kinase Activation and the Transactivator Activating Transcription Factor 3 Endocrinology, February 1, 2008; 149(2): 783 - 792. [Abstract] [Full Text] [PDF]

				W. B. Denny, V. Prapapanich, D. F. Smith, and J. G. Scammell Structure-Function Analysis of Squirrel Monkey FK506-Binding Protein 51, a Potent Inhibitor of Glucocorticoid Receptor Activity Endocrinology, July 1, 2005; 146(7): 3194 - 3201. [Abstract] [Full Text] [PDF]

				T. R. Hubler, W. B. Denny, D. L. Valentine, J. Cheung-Flynn, D. F. Smith, and J. G. Scammell The FK506-Binding Immunophilin FKBP51 Is Transcriptionally Regulated by Progestin and Attenuates Progestin Responsiveness Endocrinology, June 1, 2003; 144(6): 2380 - 2387. [Abstract] [Full Text] [PDF]

				W. B. Denny, D. L. Valentine, P. D. Reynolds, D. F. Smith, and J. G. Scammell Squirrel Monkey Immunophilin FKBP51 Is a Potent Inhibitor of Glucocorticoid Receptor Binding Endocrinology, November 1, 2000; 141(11): 4107 - 4113. [Abstract] [Full Text] [PDF]

				S. K. Mahata, M. Mahata, C. V. Livsey, H.-H. Gerdes, W. B. Huttner, and D. T. O’Connor Neuroendocrine Cell Type-Specific and Inducible Expression of the Secretogranin II Gene: Crucial Role of Cyclic Adenosine Monophosphate and Serum Response Elements Endocrinology, February 1, 1999; 140(2): 739 - 749. [Abstract] [Full Text]

				L. C. Jones and J. G. Scammell The cAMP-response element mediates induction of secretogranin II by CHX and FSK in GH4C1 cells Am J Physiol Endocrinol Metab, April 1, 1998; 274(4): E656 - E664. [Abstract] [Full Text] [PDF]

				L. Canaff, S. Bevan, D. G. Wheeler, A. J. Mouland, R. P. Rehfuss, J. H. White, and G. N. Hendy Analysis of Molecular Mechanisms Controlling Neuroendocrine Cell Specific Transcription of the Chromogranin A Gene Endocrinology, March 1, 1998; 139(3): 1184 - 1196. [Abstract] [Full Text] [PDF]