COMPARISON OF THE EXPRESSION AND FUNCTION OF THE TRANSCRIPTION FACTORPU.1 (SPI-1 PROTOONCOGENE) BETWEEN MURINE MACROPHAGES AND B-LYMPHOCYTES

The expression of mRNA encoding the DNA-binding protein PU.1(Spi-1) is restricted to B lymphocytes and macrophages. The role of PU.1 in tiss ue-specific transcriptional regulation in the two cell types was exami ned by co-transfection of a PU.1 expression plasmid with vectors conta ining B cell (IgH enhancer) or macrophage-specific (c-fms) transcripti on control elements. Cotransfection of the PU.1 expression plasmid in MOPC31C B cells trans-repressed the IgH enhancer but trans-activated t he c-fms promoter. The latter was insufficient to overcome a block to transcription elongation that determines macrophage-specific c-fms gen e expression. In the macrophage line RAW264, PU.1 had no effect on the c-fms promoter, but trans-repressed the activity of a c-fms reporter plasmid containing the transcription attenuator. The effects of PU.1 i n both cell types were distinct from those of c-ets-2, a related facto r, which trans-activated the c-fms promoter in both B cells and macrop hages but also repressed the IgH enhancer. PU.1 was shown to be one of several nuclear proteins that bound a critical cis-acting element of the IgH enhancer, mu B, but analysis of nuclear extracts of a wide ran ge of B cell and macrophage lines demonstrated a strong correlation be tween macrophage phenotype and nuclear PU.1 expression. The data sugge st that differences in nuclear PU.1 expression and function between ma crophages and B cells may play a role in lineage divergence.