Neuroendocrine cell type-specific and inducible expression of chromogranin/secretogranin genes: crucial promoter motifs

Abstract

The chromogranin/secretogranins (Cg/Sg) are a family of soluble, acidic proteins representing major constituents in secretory vesicle cores of virtually all neuroendocrine tissues. We and others have identified the cyclic adenosine monophosphate response element (CRE) as the crucial promoter element responsible for neuroendocrine cell type-specific expression of the Cg/Sg genes. In addition to CRE, GC-rich domains in chromogranin B (CgB) and serum response element (SRE) in secretogranin II (SgII) promoters appear to play important roles in neuroendocrine cell type-specific expression of CgB and SgII genes. Nicotinic-cholinergic and peptidergic chromaffin cell stimuli evoke catecholamine secretion and augment biosynthesis of Cg/Sg genes. These stimuli signal to CgA gene transcription through the CRE in cis and through protein kinase A, protein kinase C, and mitogen-activated protein kinase and CRE-binding protein in trans. In addition to CRE, a GC-rich domain in CgB and SRE in SgII promoters also play important roles in mediating inducible expression of the CgB and SgII genes. We conclude that CRE, GC-rich domains, and SRE are crucial determinants of both cell type-specific and secretagogue-inducible expression of the Cg/Sg genes.