Neuroendocrine cell type-specific and inducible expression of the secretogranin II gene: Crucial role of cyclic adenosine monophosphate and serum response elements

Secretogranin II, an acidic protein in the chromogranin/secretogranin famil y, is widely distributed in neuroendocrine secretory granules. What factors govern such widespread, yet selective, expression? The 5' deletions locali zed neuroendocrine cell type-specific expression to the proximal mouse secr etogranin II promoter: such expression was abolished after deletion past th e cAMP response element(CRE; [-67 bp]TGACGTCA[-60 bp]), and transfer of the CRE to a neutral promoter conferred 3.4- to 5.3-fold neuroendocrine select ivity. Thus, the CRE is, at least partly, sufficient to confer tissue-speci fic expression. Substantial (48-59%) loss of cell type-specific expression also occurred upon deletion past the serum response element (SRE; [-302 bp] GATGTCC[-296 bp]), and transfer of the SRE to a neutral pro meter also conf erred neuroendocrine selectivity. Expression of both the endogenous gene an d the transfected secretogranin II promoter was up-regulated after secretag ogues, and the degree of trans-activation of the transfected promoter (2.2- to 5.4-fold) paralleled activation of the endogenous gene (1.8- to 3.2-fol d). The 5' promoter deletions revealed complete loss of secretagogue respon ses after deletion past the CRE. Transfer of the CRE to a neutral promoter conferred secretagogue responses (by 2.2- to 18.6-fold). Substantial (59-74 %) falls in secretagogue responses also occurred after deletion past the pr omoter's SRE. Transfer of the SRE to a neutral promoter conferred secretago gue responses (by 2.7- to 8.3-fold). We conclude that the CRE is a crucial determinant of cell type-specific constitutive and secretagogue-inducible e xpression of the secretogranin II gene and that the SRE also plays a substa ntial role in both processes.