Mierendorf R C, Mueller G C
J Biol Chem. 1981 Jul 10;256(13):6736-41.
The expression of the globin genes which accompanies the chemically induced differentiation of Friend erythroleukemia cells is subject to inhibition by glucocorticoid hormones. The present study inquires into the possible mechanisms for this suppression. It is shown that the synthetic glucocorticoid, dexamethasone, can both prevent the initial appearance of beta-globin mRNA during the induction of differentiation and inhibit the ongoing production of this RNA in induced cells. Isolated nuclei from dexamethasone-treated cells also exhibited a depressed ability to synthesize beta-globin mRNA. These effects were achieved without altering the turnover rate of the mature messenger RNA. Electrophoretic analysis of pulse-labeled transcripts before and after a chase interval indicated that large Mr beta-globin precursor molecules were processed normally to mature nuclear beta-globin mRNA in cells treated with dexamethasone. S1 nuclease protection experiments showed further that dexamethasone treatment of induced cells uniquely depressed the amount of precursor-specific beta-globin sequences contained in unlabeled nuclear RNA preparations. The data support the view that dexamethasone regulates globin gene expression at or very close to the transcriptional level.
伴随化学诱导的弗氏红白血病细胞分化而出现的珠蛋白基因表达，会受到糖皮质激素的抑制。本研究探讨了这种抑制作用的可能机制。结果表明，合成糖皮质激素地塞米松既能在诱导分化过程中阻止β-珠蛋白mRNA的最初出现，又能抑制诱导细胞中该RNA的持续产生。从用地塞米松处理过的细胞中分离出的细胞核，合成β-珠蛋白mRNA的能力也有所降低。这些效应是在不改变成熟信使RNA周转率的情况下实现的。对追踪间隔前后脉冲标记转录本的电泳分析表明，在用地塞米松处理的细胞中，大分子量的β-珠蛋白前体分子能正常加工成成熟的核β-珠蛋白mRNA。S1核酸酶保护实验进一步表明，用地塞米松处理诱导细胞会独特地降低未标记核RNA制剂中包含的前体特异性β-珠蛋白序列的量。这些数据支持这样一种观点，即地塞米松在转录水平或非常接近转录水平上调节珠蛋白基因的表达。
