NONKILLER CELL-SPECIFIC TRANSCRIPTION FACTORS SILENCE THE PERFORIN PROMOTER

Perforin is a pore-forming killer protein exclusively expressed by cel ls functionally defined as cytolytic lymphocytes. Previous reporter ge ne investigations have indicated that the cell-type-specific expressio n of the perforin gene is determined by the promoter and upstream regi on but the respective cis- and trans-acting molecules remain to be ide ntified. In this investigation, we differentially display DNA-protein interactions of perforin-positive vs perforin-negative cell types and functionally test their biological relevance. Our results provide mole cular evidence for the transcriptional repression of the perforin gene in non-kilter cells by two novel regulatory elements. One of the resp ective transcription factors that are exclusively expressed by non-kil ler cells appears to be an Ets family member. Thus, the development of cells expressing perforin, and perhaps cytolytic lymphocytes in gener al, may involve a shutdown of the genes for these proteins.