title: Non-killer cell-specific transcription factors silence the perforin promoter.
abstract: Perforin is a pore-forming killer protein exclusively expressed by cells functionally defined as cytolytic lymphocytes. Previous reporter gene investigations have indicated that the cell-type-specific expression of the perforin gene is determined by the promoter and upstream region but the respective cis- and trans-acting molecules remain to be identified. 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 molecular evidence for the transcriptional repression of the perforin gene in non-killer cells by two novel regulatory elements. One of the respective transcription factors that are exclusively expressed by non-killer cells appears to be an Ets family member. Thus, the development of cells expressing perforin, and perhaps cytolytic lymphocytes in general, may involve a shutdown of the genes for these proteins.
authors.affiliation: Department of Microbiology and Immunology, University of Miami School of Medicine, FL 33101, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: M G
authors.initials: MG
authors.lastname: Lichtenheld
mesh_terms: D000818:Animals; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D018983:DNA Footprinting; D004268:DNA-Binding Proteins / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000276:immunology; D051379:Mice; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000378:metabolism; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D011401:Promoter Regions, Genetic / Q000187:drug effects* / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D004268:DNA-Binding Proteins; D008562:Membrane Glycoproteins; D009687:Nuclear Proteins; D052899:Pore Forming Cytotoxic Proteins; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D054353:Perforin; D004247:DNA