The Pmed1 Gene Promoter of Human FcγRIIIA Can Function as a NK/T Cell-Specific Restriction Element, Which Involves Binding of Sp1 Transcription Factor

Abstract

The low-affinity receptor for IgG (human FcγRIIIA) is selectively expressed by a subset of T lymphocytes, NK cells, and macrophages. To understand the mechanisms underlying this pattern of cell type-specific expression, we initially identified alternative promoters, Pmed1/2 and Pprox, in the 5′ end of the FcγRIIIA gene. In this study, we focused on the Pmed1 promoter and demonstrated this 93-bp region to be highly specific in governing restriction to NK/T cell lines. This property of Pmed1 is context independent and can extend to a disparate promoter. Deletion analysis defined a contribution of two separate elements located to the 5′ 21-bp (−942/−922) and 3′ 72-bp (−921/−850) regions of Pmed1 in conferring NK/T cell specificity. The 5′ part of Pmed1 contains binding sites for Sp1 and NK element-recognizing factors and substitution mapping studies revealed a critical requirement of the Sp1-I site. The importance of Sp1 protein to regulate maximal Pmed1 promoter activity was further established by EMSAs and cotransfection experiments in Sp1-null Drosophila SL2 cells. Our data suggest that Sp1 can contribute, in part, to NK/T cell restriction and further indicate that the FcγRIIIA Pmed1 sequence might be useful to direct the NK/T cell-specific expression of heterologous genes.