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Volume 271, Number 48, Issue of November 29, 1996 pp. 30755-30764
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

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

(Received for publication, May 22, 1996)

From the Department of Clinical Immunology, Hannover Medical School, Konstanty-Gutschow Strae 8, 30625 Hannover, Federal Republic of Germany

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 FcRIII, CD16) encoded by the FcRIII-A gene. Here we report that the Pprox promoter (198/10) of FcRIII-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 FcRIII-A a2/3 and a5/6 splice alternatives in NK cells were mapped to the medial 1817/850 FcRIII-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 FcRIII-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.

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