Involvement of the transcription factor PU.1/Spi-1 in myeloid cell-restricted expression of an interferon-inducible gene encoding the human high-affinity Fc gamma receptor.
Induction by gamma interferon (IFN-gamma) of the gene encoding the human high-affinity Fc gamma receptor (Fc gamma R1) in myeloid cells requires an IFN-gamma response region (GRR) and a myeloid cell-activating transcription element (MATE). GRR and MATE interact with factors to form, 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. Sequence analysis of a cDNA encoding a polypeptide recognizing specifically the MATE motif led to the identification of this product as the proto-oncogene PU.1/Spi-1, a transcriptional activator expressed in myeloid and B cells. Expression of this factor in nonhematopoietic cells allowed 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 mechanism leading to cell-type-restricted and IFN-induced gene expression.
Unité 365 INSERM, Institut Curie, Paris, France.
C
C
Perez
E
E
Coeffier
F
F
Moreau-Gachelin
J
J
Wietzerbin
P D
PD
Benech
D001402:B-Lymphocytes / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D007951:Leukemia, Myeloid / Q000378:metabolism*; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger / Q000235:genetics; D017452:Receptors, IgG / Q000235:genetics*; D011994:Recombinant Proteins; D012045:Regulatory Sequences, Nucleic Acid; D015682:Retroviridae Proteins, Oncogenic
D004268:DNA-Binding Proteins; D007370:Interferon Type I; C000715470:MAS1 protein, human; D046911:Macromolecular Substances; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D017452:Receptors, IgG; D011994:Recombinant Proteins; D015682:Retroviridae Proteins, Oncogenic; C062022:v-Spi-1 protein, Friend spleen focus-forming virus; D007371:Interferon-gamma