MOUSE BETA-GLOBIN DNA-BINDING PROTEIN B1 IS IDENTICAL TO A PROTOONCOGENE, THE TRANSCRIPTION FACTOR SPI-1 PU.1, AND IS RESTRICTED IN EXPRESSION TO HEMATOPOIETIC-CELLS AND THE TESTIS/

The hematopoietic-specific DNA-binding protein B1 binds to the DNA con sensus sequence AAAGRGGAARYG located twice in intervening sequence 2 o f both of the mouse beta-globin genes (D. L. Galson and D. E. Housman, Mol. Cell. Biol. 8:381-392, 1988). B1 was cloned by expression of a m urine erythroleukemia (MEL) cell cDNA library in transfected COS cells and screening by electrophoretic mobility shift analysis. B1 is ident ical to the proto-oncogene Spi-1/PU.1 (Spi-1), an ets family member. P rotein-DNA contacts are shown to resemble those of the helix-turn-heli x homeodomain proteins. By Northern (RNA) analysis, we found that Spi- 1 mRNA is present at low levels during murine CFU-E maturation and is at least 20-fold higher in uninduced MEL, a transformed proerythroblas t-like cell line which contains an activating/transforming insertion o f spleen focus-forming virus at the Spi-1 locus. Dimethyl sulfoxide-in duced MEL cell differentiation decreases Spi-1 mRNA to approximately 2 0% of the uninduced level before commitment occurs. In addition to ery throid cells, Spi-1 mRNA is present in B cells, myelomonocytes, and ma st cells but not in T cells and nonhematopoietic cell types. In situ h ybridization demonstrated Spi-1 mRNA expression in bone marrow, spleen , interstitial nonhepatocytes of the liver, and interstitial nontubula r cells of the testis. The Spi-1 locus was mapped on human chromosome 11 to the same interval as ACP2 (lysosomal acid phosphatase), between the anonymous DNA markers D11S33 and D11S14. This region has not yet b een found to be associated with a human malignancy.