Complex Cell Type-Specific Transcriptional Regulation by the Promoter and an Intron of the Mouse P-Cadherin Gene. (P-cadherin/cell adhesion molecule/transcriptional regulation)

Abstract

Expression of cell-cell adhesion molecule cadherins is dynamically regulated during development. We describe the structure of the promoter of the mouse P-cadherin gene and its transcriptional activity. The P-cadherin promoter had a tandem of B2 repetitive elements showing structural similarities to the E-cadherin gene promoter. Transcriptional properties of the P-cadherin promoter were surveyed along about 10 kbp of the 5° flanking region by CAT assay in several cell lines expressing or not expressing P-cadherin mRNA. The P-cadherin promoter exhibited complex profiles of transcriptional activity. When the promoter was introduced into P-cadherin positive cell lines, its activity greatly varied with the cell lines. Moreover, this promoter was active even in some of P-cadherin negative cell lines. Analyses of 5° deletions of the promoter suggest that multiple elements are differentially used by different cell lines. We also detected enhancer-like elements in the 2nd intron, which can activate both the P-cadherin and thymidine kinase promoters. The activity of each enhancer varied with cell lines, being independent of endogenous P-cadherin expression. These results suggest that P-cadherin gene transcription is regulated by highly complex combinations of elements in the promoter and the 2nd intron studied here and other regions for the cell-type specific expression.