Shannon M F, Gamble J R, Vadas M A
Division of Human Immunology, Institute of Medical and Veterinary Science, Adelaide, South Australia.
Proc Natl Acad Sci U S A. 1988 Feb;85(3):674-8. doi: 10.1073/pnas.85.3.674.
The gene for human granulocyte/macrophage colony-stimulating factor (GM-CSF) is expressed in a tissue-specific as well as an activation-dependent manner. The interaction of nuclear proteins with the promoter region of the GM-CSF gene that is likely to be responsible for this pattern of GM-CSF expression was investigated. We show that nuclear proteins interact with DNA fragments from the GM-CSF promoter in a cell-specific manner. A region spanning two cytokine-specific sequences, cytokine 1 (CK-1, 5' GAGATTCCAC 3') and cytokine 2 (CK-2, 5' TCAGGTA 3') bound two nuclear proteins [nuclear factor (NF)-GMa and NF-GMb] from GM-CSF-expressing cells in gel retardation assays. NF-GMb was inducible with phorbol 12-myristate 13-acetate and accompanied induction of GM-CSF message. NF-GMb was absent in cell lines not producing GM-CSF, some of which had other distinct binding proteins. NF-GMa and NF-GMb eluted from a heparin-Sepharose column at 0.3 and 0.6 M KCl, respectively. We hypothesize that the sequences CK-1 and CK-2 bind specific proteins and regulate GM-CSF transcription.
人类粒细胞/巨噬细胞集落刺激因子（GM-CSF）基因以组织特异性以及激活依赖性方式表达。我们研究了核蛋白与GM-CSF基因启动子区域的相互作用，这种相互作用可能是造成GM-CSF这种表达模式的原因。我们发现核蛋白以细胞特异性方式与GM-CSF启动子的DNA片段相互作用。在凝胶阻滞试验中，一个跨越两个细胞因子特异性序列（细胞因子1，CK-1，5' GAGATTCCAC 3'；细胞因子2，CK-2，5' TCAGGTA 3'）的区域结合了来自表达GM-CSF细胞的两种核蛋白[核因子（NF）-GMa和NF-GMb]。NF-GMb可被佛波醇12-肉豆蔻酸酯13-乙酸酯诱导，并伴随GM-CSF信使的诱导。在不产生GM-CSF的细胞系中不存在NF-GMb，其中一些细胞系有其他不同的结合蛋白。NF-GMa和NF-GMb分别在0.3和0.6 M KCl浓度下从肝素-琼脂糖柱上洗脱。我们推测序列CK-1和CK-2结合特定蛋白并调节GM-CSF转录。
