NOVEL TRANSCRIPTIONAL MECHANISMS ARE INVOLVED IN REGULATING PREPROENKEPHALIN GENE-EXPRESSION IN-VIVO

For the dissection of the temporal and spatial patterns of cell-and ti ssue-specific gene expression an understanding of the contributing reg ulating mechanisms is required. We now confirm that there are novel me chanisms regulating preproenkephalin gene expression in basal as well as cholinergic agonist treated rats. Moreover, we demonstrate that the se novel transcriptional mechanisms are consistent with RNA intragenic elongation pausing, alternate promoter usage, and small sense and ant isense RNA transcription from the preproenkephalin gene locus. We repo rt that while basal striatal and olfactory bulb proenkephalin RNA tran scripts are initiated from the ''normal'' proximal promoter, in cerebe llum de novo RNA transcription appears to be initiated from the distal so-called ''germ-cell'' promoter. Furthermore, ''normally'' initiated olfactory bulb proenkephalin RNA transcripts appear to be down-regula ted by the time the RNA polymerase II complex reaches the first prepro enkephalin intron, in a way that is consistent with RNA elongation pau sing. As the pattern of small sense and antisense transcripts found as sociated with this gene's expression is tissue-specific, we suggest th at they may also play a role in regulating gene expression. The under standing of this gene's regulation should have widespread importance, not only to those interested in opioid gene expression, but also to th ose interested in gene regulation, in general. (C) 1998 Academic Press .