A COMPOSITE DNA ELEMENT IN THE PROMOTER OF THE POLYMERIC IMMUNOGLOBULIN RECEPTOR REGULATES ITS CONSTITUTIVE EXPRESSION

The polymeric immunoglobulin receptor (plgR), which is constitutively expressed on the basolateral surface of secretory epithelial cells, me diates external translocation of polymeric IgA and pentameric IgM (col lectively called pig) to exocrine secretions. A high level of synthesi s must be maintained because the receptor is continuously cleaved to r elease bound secretory component (SC) in secretory IgA and secretory I gM, as well as free SC from unoccupied receptor. We have isolated the promoter of the plgR gene ano identified a short activating region tha t is required for the expression of plgR promoter-driven reporter gene s. This region contained an E-box and an inverted repeat sequence (IRS ). Gel electrophoresis mobility shift assays with nuclear extracts fro m different plgR-expressing epithelial cell lines demonstrated protein s that bind independently to both the E-box and the IHS sequence of th e plgR promoter. In addition, a DNA probe that contained both the E-bo x and the IHS gave rise to a larger complex that could not be competed by either element on its own. Binding was confirmed by DNase I footpr inting of the E-box and IRS sequences with nuclear extracts, and by di methyl sulfide footprinting in living HT-29 epithelial cells. Finally, a mutation in the plgR promoter that inhibited protein binding to the E-box and the formation of the larger complex, abolished activated tr anscription from the reporter gene.