IFN-gamma and lipopolysaccharide induce DNA binding of transcription factor PU.1 in murine tissue macrophages.

The transcription factor PU.1, the Spi-1 oncogene product, is found principally in B cells and macrophages. PU.1 binds to a purine-rich sequence of DNA with a core consensus sequence of 5'-GAGGAA-3'. By using an electrophoretic mobility shift assay, we have been able to identify PU.1 in nuclear extracts of murine tissue macrophages. When macrophages are stimulated with IFN-gamma, an increase in PU.1 binding is observed. This increase is gradual, peaking at 6 to 9 h and decaying to basal levels 24 h after stimulation. The increase in PU.1 binding is unaffected by inhibiting protein synthesis, but is attenuated by either an inhibitor of the NA+/H+ antiporter or elevations in cAMP. In addition, we have found that low doses (1 ng/ml) of bacterial LPS induce PU.1 binding.