Complex Cell Type‐Specific Transcriptional Regulation by the Promoter and an Intron of the Mouse P‐Cadherin Gene

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.