ISOLATION AND GENOMIC ANALYSIS OF THE RAT POLYMERIC IMMUNOGLOBULIN RECEPTOR GENE TERMINAL DOMAIN AND TRANSCRIPTIONAL CONTROL REGION

The polymeric immunoglobulin receptor (pIgR) transports IgA and IgM ac ross secretory epithelial cells and is essential in external immunity maintenance, We report here the structural characterization of the sin gle-copy rat gene distributed over 30 kb of chromosomal DNA and analys is of its transcriptional control region, RNA sequencing and genomic a nalysis show a 5' terminal region originates at a major (+1) and a min or site producing an unusual 124-bp nontranslated exon I separated fro m a small 96-bp initiator ATG coding exon II by a 7,5-kb intron. The p IgR 5' region comprises a structured promoter with abundant helix-loop -helix (bHLH) cis elements positioned within an equivalent internal -7 0, -290, -528, and three centered at -745. The three latter bHLH eleme nts each occur within 30-bp repeats at -690 to -780, Transient express ion assays show a 1,3-kb 5' region is sufficient to drive expression i n rat primary hepatocyte monolayer cultures, transformed human hepatic (HepG2) cells, and a mammary epithelial tumor cell line MCF-7, but is inactive in the rodent fibroblast 3T3 cell line, A minimal transcript ional promoter domain was deduced from sequentially deleted vectors re vealing a +40 to -922 sequence to be sufficient for full activity. Fur ther deletions within this region yield incremental losses in cis acti vity, indicating that multiple subregions comprise an extended transcr iptional control region.