Separate promoters from proximal and medial control regions contribute to the natural killer cell-specific transcription of the human FcgammaRIII-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 FcgammaRIII, CD16) encoded by the FcgammaRIII-A gene. Here we report that the Pprox promoter (-198/-10) of FcgammaRIII-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 FcgammaRIII-A a2/3 and a5/6 splice alternatives in NK cells were mapped to the medial -1817/-850 FcgammaRIII-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 FcgammaRIII-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.
Gessner
J E
JE
Department of Clinical Immunology, Hannover Medical School, Konstanty-Gutschow Strabetae 8, 30625 Hannover, Federal Republic of Germany.
Grussenmeyer
T
T
Dumbsky
M
M
Schmidt
R E
RE
D017398:Alternative Splicing; D001483:Base Sequence; D005796:Genes; D006801:Humans; D007694:Killer Cells, Natural / Q000502:physiology*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D017452:Receptors, IgG / Q000235:genetics*; D017384:Sequence Deletion; D014158:Transcription, Genetic
D012333:RNA, Messenger; D017452:Receptors, IgG