EXPRESSION OF THE TRANSCRIPTION FACTOR, SPI-1 (PU.1), IN DIFFERENTIATING MURINE ERYTHROLEUKEMIA-CELLS IS REGULATED POSTTRANSCRIPTIONALLY - EVIDENCE FOR DIFFERENTIAL STABILITY OF TRANSCRIPTION FACTOR MESSENGER-RNAS FOLLOWING INDUCER EXPOSURE

Increased expression of the transcription factor Spi-1 (PU.1) results from retroviral insertion in nearly all Friend spleen focus-forming vi rus-transformed murine erythroleukemia cell lines and exposure of thes e cells to Me(2)SO, induces their differentiation and decreases Spi-1 mRNA level by 4-5-fold. While these results suggest that alterations i n Spi-1 expression have significant effects on erythroblast growth and differentiation, neither the cause nor the effect of the decrease in Spi-1 expression that follows Me(2)SO exposure has been established. T he experiments described here demonstrate that the effect of inducers on Spi-1 expression is regulated post-transcriptionally. Nuclear run-o ff transcriptions demonstrated that Spi-1 transcription was not decrea sed following Me(2)SO exposure. Additionally, expression of a recombin ant Spi-1 mRNA under transcriptional control of a constitutively activ e Rous sarcoma virus promoter was regulated identically to endogenous Spi-1 mRNA. The ability of Me(2)SO to destabilize Spi-1 mRNA was selec tive, as the stability of the erythroid transcription factors GATA-1 a nd NF-E2 were not similarly effected. The effect of Me(2)SO on the sta bility of Spi-1 mRNA provides a novel means of altering gene expressio n in these cells and is likely to have significance for the differenti ation of these cells.