Arai N, Nomura D, Villaret D, DeWaal Malefijt R, Seiki M, Yoshida M, Minoshima S, Fukuyama R, Maekawa M, Kudoh J
Department of Molecular Biology, DNAX Research Institute, Palo Alto, CA 94304-1104.
J Immunol. 1989 Jan 1;142(1):274-82.
We have isolated a chromosomal DNA segment of the human IL-4 gene based on homology with a human IL-4 cDNA sequence and determined its complete nucleotide sequence. The human IL-4 gene, which occurs as a single copy in the haploid genome, is mapped on chromosome 5. It is composed of four exons and three introns and is approximately 10 kilobase pairs in size. 5'-Flanking regions of human and mouse IL-4 genes share about 85% homology extending more than 500 base pairs upstream of a "TATA" like sequence. Several patches of sequences are found in the 5'-flanking region of the human IL-4 gene which are homologous to sequence in the 5'-flanking regions of the IL-2, IL-3, IL-5, and granulocyte-macrophage (GM)-CSF genes. The IL-4 gene is inducible after treatment of human T cell clone by phorbol-12-myristate-13-acetate (TPA) and calcium ionophore A23187. The 2.3-kb 5'-flanking region of the human IL-4 gene transiently transfected into Jurkat human T cell leukemia cells is activated efficiently in response to TPA and A23187 stimulation and, although less efficiently, by human T cell leukemia virus type I-encoded p40x or BPV-encoded E2 protein. Combination of TPA/A23187 and p40x or E2 protein further augmented the level of expression.
我们基于与人白细胞介素-4(IL-4)cDNA序列的同源性,分离出了人IL-4基因的一段染色体DNA片段,并确定了其完整的核苷酸序列。人IL-4基因在单倍体基因组中以单拷贝形式存在,定位于5号染色体上。它由四个外显子和三个内含子组成,大小约为10千碱基对。人和小鼠IL-4基因的5'侧翼区域具有约85%的同源性,在类似“TATA”序列上游延伸超过500个碱基对。在人IL-4基因的5'侧翼区域发现了几个与IL-2、IL-3、IL-5和粒细胞-巨噬细胞(GM)-集落刺激因子(CSF)基因的5'侧翼区域序列同源的片段。用佛波醇-12-肉豆蔻酸酯-13-乙酸酯(TPA)和钙离子载体A23187处理人T细胞克隆后,IL-4基因可被诱导。瞬时转染到Jurkat人T细胞白血病细胞中的人IL-4基因的2.3 kb 5'侧翼区域,在受到TPA和A23187刺激时能有效激活,并且虽然效率较低,但也能被I型人T细胞白血病病毒编码的p40x或牛乳头瘤病毒(BPV)编码的E2蛋白激活。TPA/A23187与p