Regulation of expression of the human interferon gamma gene.
Regulation of expression of the human interferon gamma gene.
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人干扰素γ基因表达的调节。
DOI：
10.1073/pnas.82.23.8173
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发表时间：
1985
影响因子：
11.1
通讯作者：
Stobo,JD
中科院分区：
文献类型：
--
作者：
Hardy,KJ;Peterlin,BM;Atchison,RE;Stobo,JD
从人γ干扰素（IFN-γ）的基因组克隆以及IFN-γ cDNA中分离的DNA片段用于通过DNase I-超敏反应分析绘制IFN-γ基因的潜在调控区域。在来自人T细胞系Jurkat的细胞核中，其可以被诱导表达IFN-γ基因，我们观察到在第一间插序列中的强烈超敏位点，其定位于基因中唯一的顺反子内重复元件。将Jurkat细胞的DNA酶I图谱与包括B细胞、巨噬细胞和上皮细胞在内的几种其他细胞类型的DNA酶I图谱进行比较。仅在能够表达IFN-γ基因的细胞中发现存在强烈的内含子超敏反应。在该基因的3'区未发现超敏反应。此外，当分析来自Jurkat的纯化基因组DNA时，没有观察到超敏反应，这表明DNA-蛋白质相互作用，而不仅仅是DNA序列，是DNA酶I超敏反应的原因。序列AAGTGTAATTTTTTGAGTTTCTTTT直接位于IFN-γ的内含子超敏区，与白细胞介素2基因5'侧翼区的几乎相同的序列具有83%的同源性。在白细胞介素2中，同源序列位于该基因启动子上游约300个碱基对处，该区域具有潜在的调节重要性。
DNA fragments isolated from a genomic clone of human gamma interferon (IFN-gamma) as well as IFN-gamma cDNA were used to map potential regulatory regions of the IFN-gamma gene by DNase I-hypersensitivity analyses. In nuclei from the human T-cell line Jurkat, which can be induced to express the IFN-gamma gene, we observed a strongly hypersensitive site in the first intervening sequence that localized to the only intracistronic repeat element in the gene. DNase I mapping of Jurkat cells was compared to that of several other cell types, including B cells, macrophages, and epithelial cells. The presence of strong intronic hypersensitivity was found only in cells capable of expressing the IFN-gamma gene. No hypersensitivity was found in the 3' regions of the gene. Further, no hypersensitivity was observed when purified genomic DNA from Jurkat was analyzed, suggesting that DNA-protein interactions, and not simply DNA sequence alone, were responsible for DNase I hypersensitivity. The sequence AAGTGTAATTTTTTGAGTTTCTTTT, which is directly in the intronic hypersensitive area of IFN-gamma, is 83% homologous to a nearly identical sequence in the 5' flanking region of the interleukin 2 gene. In interleukin 2, the homologous sequence is about 300 base pairs upstream of that gene's promoter in an area of potential regulatory importance.