Separate Promoters from Proximal and Medial Control Regions Contribute to the Natural Killer Cell-specific Transcription of the Human FcγRIII-A (CD16-A) Receptor Gene

The molecular events governing the differentiation pathway of natural killer (NK) cells are not well understood. The phenotype of mature NK cells is specified by the expression of the low affinity Fc receptor for IgG (human FcγRIII, CD16) encoded by the FcγRIII-A gene. Here we report that the Pprox promoter (−198/−10) of FcγRIII-A stimulated by its own intron enhancer (+10/+712) was only one of the cis-elements that target the expression of a reporter gene in the immature NK cell line, YT. The transcription start sites of the FcγRIII-A a2/3 and a5/6 splice alternatives in NK cells were mapped to the medial −1817/−850 FcγRIII-A control region. Two promoters, Pmed1 (−942/−850) and Pmed2 (−1376/−1123) resided in this region and controlled for the initiation of these transcript classes encoding the known FcγRIII-A receptor protein. Deletion mapping studies demonstrated that the 93 base pairs −942/−850 Pmed1 sequence was sufficient to confer cell type-specific expression in YT cells. The 5′ end of Pmed1 (−942 to −921) was required for full promoter function indicating the presence of an important sequence motif recognized by a YT-specific factor. Our data suggest that this motif might be a useful tool for subsequent identification of putative transcription factors uniquely active in YT and NK cells. The molecular events governing the differentiation pathway of natural killer (NK) cells are not well understood. The phenotype of mature NK cells is specified by the expression of the low affinity Fc receptor for IgG (human FcγRIII, CD16) encoded by the FcγRIII-A gene. Here we report that the Pprox promoter (−198/−10) of FcγRIII-A stimulated by its own intron enhancer (+10/+712) was only one of the cis-elements that target the expression of a reporter gene in the immature NK cell line, YT. The transcription start sites of the FcγRIII-A a2/3 and a5/6 splice alternatives in NK cells were mapped to the medial −1817/−850 FcγRIII-A control region. Two promoters, Pmed1 (−942/−850) and Pmed2 (−1376/−1123) resided in this region and controlled for the initiation of these transcript classes encoding the known FcγRIII-A receptor protein. Deletion mapping studies demonstrated that the 93 base pairs −942/−850 Pmed1 sequence was sufficient to confer cell type-specific expression in YT cells. The 5′ end of Pmed1 (−942 to −921) was required for full promoter function indicating the presence of an important sequence motif recognized by a YT-specific factor. Our data suggest that this motif might be a useful tool for subsequent identification of putative transcription factors uniquely active in YT and NK cells.