NEUTROPHILS AND MONOCYTES EXPRESS HIGH-LEVELS OF PU.1 (SPI-1) BUT NOTSPI-B

PU.1 (the Spi-1 oncogene) and Spi-B are closely related members of the ets transcription factor family, sharing similar DNA binding specific ities mediated by similar DNA binding domains. PU.1 and Spi-B have bee n previously described as being predominantly expressed coordinately i n macrophages and B cells, but their expression in early hematopoietic stages and during the course of myeloid differentiation to monocytes and macrophages or to neutrophils has not been extensively investigate d. Here, we report that PU.1 mRNA is upregulated during myeloid differ entiation of human purified CD34(+) cells and murine multipotential FD CP-mix A4 cells, suggesting that PU.1 is upregulated as an early event during differentiation of multipotential progenitor cells. PU.1 expre ssion is maintained at stable levels during differentiation of myeloid cell lines U937 and HL-60 to monocytic and neutrophilic cells. PU.1 i s expressed at highest levels in mature human monocytes and human peri pheral blood neutrophils. In contrast to PU.1, significant levels of S pi-B mRNA and protein are found only in some B-cell lines and spleen b ut are not found in myeloid cell lines, neutrophils, or macrophages. I n vitro translated Spi-B protein can bind to PU.1 binding sites in mye loid promoters and transactivate these promoters in nonmyeloid cells. Therefore, although PU.1 and Spi-B may bind to similar DNA control ele ments and have redundancy of transactivation function in vitro, the la ck of significant levels of Spi-B in myeloid cells makes it unlikely t hat Spi-B plays a significant role in myeloid lineage development and gene expression. In contrast, PU.1 is expressed at high levels not onl y in monocytes and macrophages but also in neutrophils, indicating tha t PU.1 can activate gene expression in both major myeloid lineages. (C ) 1995 by The American Society of Hematology.