Distinct functions for signal transducer and activator of transcription 1 and PU.1 in transcriptional activation of Fc gamma receptor I promoter.
The myeloid cell-specific expression and interferon-gamma (IFN-gamma) induction of Fc gamma receptor I (FcgammaRI) requires cooperation between PU.1 and signal transducer and activator of transcription 1 (Stat1) by means of mechanisms that are unknown. We found that PU.1 and Stat1 mediated distinct functions in the activation of FcgammaRI promoter. The basal activity of the natural FcgammaRI promoter was strictly dependent on PU.1, and IFN-gamma induction required both PU.1 and Stat1. Recruitment of TATA-binding protein (TBP) to the FcgammaRI promoter did not replace PU.1 in promoter activation, suggesting that TBP is not sufficient for FcgammaRI activation and that PU.1 mediates additional contacts with basal transcription machinery. In contrast, Stat1 did not interact with basal transcription machinery, but the Stat1-mediated activation of FcgammaRI promoter critically required CREB-binding protein (CBP)/p300. These results define functional cooperativity between PU.1 and Stat1 in FcgammaRI promoter activation, in which PU.1 appears to serve as a bridging factor with the basal transcription machinery and IFN-gamma-mediated induction of transcription occurs through recruitment of CBP/p300 by Stat1.
Institute of Medical Technology, University of Tampere, Finland.
Saara
S
Aittomäki
Jie
J
Yang
Edward W
EW
Scott
M Celeste
MC
Simon
Olli
O
Silvennoinen
D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D051379:Mice; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D017452:Receptors, IgG / Q000235:genetics*; D050794:STAT1 Transcription Factor; D015534:Trans-Activators / Q000502:physiology*; D014162:Transfection; D000099232:Proto-Oncogene Protein Spi-1
D004268:DNA-Binding Proteins; D007371:Interferon-gamma; D011518:Proto-Oncogene Proteins; D017452:Receptors, IgG; D050794:STAT1 Transcription Factor; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1; C494079:STAT1 protein, human; C494080:Stat1 protein, mouse