PU.1 (Spi-1) and C/EBP alpha regulate the granulocyte colony-stimulating factor receptor promoter in myeloid cells
PU.1 (Spi-1) and C/EBP alpha regulate the granulocyte colony-stimulating factor receptor promoter in myeloid cells
复制标题
DOI：
10.1182/blood.v88.4.1234.bloodjournal8841234
复制
发表时间：
1996-08-15
期刊：
影响因子：
20.3
通讯作者：
Tenen, DG
中科院分区：
文献类型：
--
作者：
Smith, LT;Hohaus, S;Tenen, DG
细胞因子对造血过程中的谱系承诺和分化很重要，通过结合特定受体发挥作用。受体表达受到严格调控，检查控制其表达的因素将有助于更好地了解决定谱系承诺的事件。粒细胞集落刺激因子（G-CSF）受体仅在髓细胞和胎盘中表达。我们在这里展示了G-CSF受体转录起始位点在这些组织中是相同的。一个1391 bp的G-CSF受体启动子片段在髓系和组织特异性中都有活性。我们还发现了两个对G-CSF受体启动子活性很重要的区域。一个位于bp -49的区域包含GCAAT位点，该位点特异性结合髓核提取物中的C/EBP α转录因子。G-CSF受体启动子的另一个重要功能区域位于5'非翻译区，位于bp +36和+43，其中有两个位点为ets家族成员PU.1。这些位点的突变阻止了PU.1的结合，并使启动子活性降低75%。这些结果强化了PU.1和C/EBP α在骨髓特异性基因表达和中性粒细胞发育中的重要性，(C) 1996年由美国血液学学会发布。
Cytokines, important for lineage commitment and differentiation during hematopoiesis, exert their influence by binding specific receptors. Receptor expression is tightly regulated and examining the factors that govern their expression will allow better understanding of the events that determine lineage commitment, The granulocyte colony-stimulating factor (G-CSF) receptor is expressed exclusively in myeloid cells and the placenta. We show here that the G-CSF receptor transcription start site is identical in each of these tissues. A 1,391-bp fragment of the G-CSF receptor promoter is both active in myeloid cell lines and tissue specific. We have also found two regions that are important for G-CSF receptor promoter activity. One region, located at bp -49, contains a GCAAT site that specifically binds the C/EBP alpha transcription factor in myeloid nuclear extracts. Mutation of this site prevents C/EBP alpha binding and reduces promoter activity by 60%, The other functionally important region of the G-CSF receptor promoter is in the 5' untranslated region, at bp +36 and +43, where there are two sites for the ets family member PU.1. Mutation of these sites prevents PU.1 binding and reduces promoter activity by 75%. These results reinforce the importance of both PU.1 and C/EBP alpha in the expression of myeloid-specific genes and neutrophil development, (C) 1996 by The American Society of Hematology.