A CELL-TYPE SPECIFIC AND ENHANCER-DEPENDENT SILENCER IN THE REGULATION OF THE EXPRESSION OF THE HUMAN UROKINASE PLASMINOGEN-ACTIVATOR GENE

A transcriptional silencer has been identified in the 5' regulatory region of the human urokinase plasminogen activator (uPA) gene. This region is able to block transcription from the human u-PA as well as the rabbit beta-globin promoters in a cell type specific and orientation independent way. The silencer is enhancer dependent and is active in two cell lines (HeLa and CV-1) which produce little if any uPA, but not in the high uPA producer PC3. Silencing activity and enhancer dependence can be separated: the silencing activity has been localized to the DNA fragment - 660 to -536, while the enhancer dependence is located in the - 536 to - 308 fragment. The DNA sequence of the silencer region contains an element that closely resembles the TGF-beta responsive negative element TIE.