Hensold J O, Stratton C A, Barth D, Galson D L
University/Ireland Cancer Center, Department of Medicine and Case Western Reserve University, Cleveland, Ohio 44106, USA.
J Biol Chem. 1996 Feb 16;271(7):3385-91. doi: 10.1074/jbc.271.7.3385.
Increased expression of the transcription factor Spi-1 (PU.1) results from retroviral insertion in nearly all Friend spleen focus-forming virus-transformed murine erythroleukemia cell lines and exposure of these cells to Me2SO, induces their differentiation and decreases Spi-1 mRNA level by 4-5-fold. While these results suggest that alterations in 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 Me2SO exposure has been established. The experiments described here demonstrate that the effect of inducers on Spi-1 expression is regulated post-transcriptionally. Nuclear run-off transcriptions demonstrated that Spi-1 transcription was not decreased following Me2SO exposure. Additionally, expression of a recombinant Spi-1 mRNA under transcriptional control of a constitutively active Rous sarcoma virus promoter was regulated identically to endogenous Spi-1 mRNA. The ability of Me2SO to destabilize Spi-1 mRNA was selective, as the stability of the erythroid transcription factors GATA-1 and NF-E2 were not similarly effected. The effect of Me2SO on the stability of Spi-1 mRNA provides a novel means of altering gene expression in these cells and is likely to have significance for the differentiation of these cells.
转录因子Spi-1（PU.1）的表达增加是由于逆转录病毒插入几乎所有Friend脾集落形成病毒转化的小鼠红白血病细胞系中，并且将这些细胞暴露于二甲亚砜（Me2SO）会诱导它们分化，并使Spi-1 mRNA水平降低4至5倍。虽然这些结果表明Spi-1表达的改变对成红细胞的生长和分化有显著影响，但Me2SO暴露后Spi-1表达降低的原因和结果均未明确。本文所述的实验表明，诱导剂对Spi-1表达的影响是在转录后水平调控的。细胞核连续转录实验表明，Me2SO暴露后Spi-1转录并未降低。此外，在组成型活性劳氏肉瘤病毒启动子转录控制下的重组Spi-1 mRNA的表达与内源性Spi-1 mRNA的调控方式相同。Me2SO使Spi-1 mRNA不稳定的能力具有选择性，因为红系转录因子GATA-1和NF-E2的稳定性未受到类似影响。Me2SO对Spi-1 mRNA稳定性的影响为改变这些细胞中的基因表达提供了一种新方法，并且可能对这些细胞的分化具有重要意义。
