Transcriptional and posttranscriptional regulation of the expression of the erythropoietin receptor gene in human erythropoietin-responsive cell lines.
Transcriptional and posttranscriptional regulation of the expression of the erythropoietin receptor gene in human erythropoietin-responsive cell lines.
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DOI：
10.1182/blood.v82.12.3760.3760
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发表时间：
1993-12
期刊：
影响因子：
20.3
通讯作者：
A. Migliaccio;Y. Jiang;Giovanni Migliaccio;S. Nicolis;Stefania Crotta;A. Ronchi;S. Ottolenghi;John W. Adamson
中科院分区：
文献类型：
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作者：
A. Migliaccio;Y. Jiang;Giovanni Migliaccio;S. Nicolis;Stefania Crotta;A. Ronchi;S. Ottolenghi;John W. Adamson
随着红细胞分化，定向祖细胞获得对促红细胞生成素（Epo）应答的能力。Epo通过Epo受体（Epo-R）与靶细胞相互作用，Epo受体的表达以谱系特异性方式受到严格调控。推测Epo-R表达随着细胞分别沿红系或髓系途径的沿着进展而被逐渐激活或抑制。很少有人知道的红细胞特异性表达的Epo-R基因的机制。加塔-1是已知的参与Epo-R基因调控的主要转录因子，它不是红系特异性的。我们已经研究了Epo-R基因在两个相关的人Epo反应细胞系UT-7和UT-7 Epo中的表达调控。这些品系由于内源基因的扩增而高水平表达Epo-R，该内源基因显然未重排。用肿瘤促进剂佛波醇肉豆蔻酸酯乙酸酯（PMA）处理6至24小时，或生长因子饥饿（Epo或粒细胞/巨噬细胞集落刺激因子[GM-CSF]）24小时，分别降低或增加Epo-R mRNA的水平。在生长因子饥饿的情况下，Epo-R mRNA水平的增加（约等于三倍）与Epo-R基因转录速率的增加直接相关，如通过径流测定所测量的。这两种增加早在生长因子撤回后3小时就观察到，并且是可逆的; mRNA水平和转录速率在细胞重新暴露于生长因子后3小时恢复到基线水平。生长因子饥饿后Epo-R表达的变化与在这些条件下在mRNA和基因转录水平上检测到的加塔-1表达水平的变化相协调（表明加塔-1负责这种上调）。在PMA处理期间，在1小时Epo-R mRNA短暂增加后，观察到Epo-R mRNA水平进行性下降; Epo-R mRNA水平下降50%，分别在6和24小时降至检测水平以下。这种递减部分地解释了四倍减少的基因转录速率以及减少（作为在放线菌素D的存在下的Epo-R mRNA的水平测量）在mRNA的稳定性。转录速率的变化发生在加塔-1结合活性水平没有变化的情况下。（400字处截断摘要）
With erythroid differentiation, committed progenitor cells acquire the ability to respond to erythropoietin (Epo). Epo interacts with target cells through the Epo receptor (Epo-R), whose expression is tightly regulated in a lineage-specific fashion. Epo-R expression is presumed to be progressively activated or repressed as cells progress along the erythroid or the myeloid pathway, respectively. Little is known of the mechanisms that underlie the erythroid-specific expression of the Epo-R gene. GATA-1, the major known transcription factor involved in Epo-R gene regulation, is not erythroid-specific. We have studied the regulation of the expression of the Epo-R gene in two related human Epo-responsive cell lines, UT-7 and UT-7 Epo. These lines express Epo-R at high levels because of amplification of the endogenous gene, which is apparently not rearranged. Treatment for 6 to 24 hours with the tumor promoter, phorbol myristate acetate (PMA), or 24 hours of growth factor starvation (Epo or granulocyte/macrophage colony-stimulating factor [GM-CSF]) decreased or increased the levels of Epo-R mRNA, respectively. In the case of growth factor starvation, the increase (approximately equal to threefold) in the level of Epo-R mRNA correlated directly with an increase in the rate of Epo-R gene transcription as measured by run-off assay. Both increases were observed as early as 3 hours after the growth factor was withdrawn and were reversible; levels of mRNA and transcription rates returned to baseline 3 hours after the cells were reexposed to growth factors. The changes in Epo-R expression after growth factor starvation were coordinated with changes in the level of expression of GATA-1 that were detected both at the mRNA and at the gene transcription level under these conditions (suggesting that GATA-1 was responsible for this upregulation). During PMA treatment, after a transient increase in Epo-R mRNA at 1 hour, a progressive decline in the level of Epo-R mRNA was observed; the level of Epo-R mRNA decreased by 50%, and fell below the level of detection by 6 and 24 hours, respectively. This decrement was explained in part by a fourfold reduction in the rate of gene transcription as well as a reduction (measured as levels of Epo-R mRNA in the presence of actinomycin D) in mRNA stability. The changes in transcription rate occurred in the absence of changes in the level of GATA-1 binding activity.(ABSTRACT TRUNCATED AT 400 WORDS)