INVOLVEMENT OF THE TRANSCRIPTION FACTOR PU.1 SPI-1 IN MYELOID CELL-RESTRICTED EXPRESSION OF AN INTERFERON-INDUCIBLE GENE ENCODING THE HUMANHIGH-AFFINITY FC-GAMMA RECEPTOR/

Induction by gamma interferon (IFN-gamma) of the gene encoding the hum an high-affinity Fc gamma receptor (Fc gamma R1) in myeloid cells requ ires an IFN-gamma response region (GRR) and a myeloid cell-activating transcription element (MATE). GRR and MATE interact with factors to fo rm, respectively an IFN-gamma-activating complex (GIRE-BP), depending on the phosphorylation of the 91-kDa protein (subunit of ISGF3), and a cell-type-specific complex (MATE-BP). Although GIRE-BP is detected in cells of different origins after IFN-gamma treatment, the presence of MATE-BP was found to be restricted to B- and myeloid cell lines. Sequ ence analysis of a cDNA encoding a polypeptide recognizing specificall y the MATE motif led to the identification of this product as the prot o-oncogene PU.1/Spi-1, a transcriptional activator expressed in myeloi d and B cells. Expression of this factor in nonhematopoietic cells all owed IFN-gamma-induced expression of a reporter gene under control of the GRR and MATE sequences. The presence of these motifs in other gene promoters indicates that the binding of PU.1/Spi-1 and IFN regulatory proteins to their respective motifs could be part of a general mechan ism leading to cell-type-restricted and IFN-induced gene expression.