Serfling E, Barthelmäs R, Pfeuffer I, Schenk B, Zarius S, Swoboda R, Mercurio F, Karin M
Institut für Virologie und Immunbiologie, Universität Würzburg, FRG.
EMBO J. 1989 Feb;8(2):465-73. doi: 10.1002/j.1460-2075.1989.tb03399.x.
The immediate upstream region of the mouse interleukin 2 (Il-2) gene harbors a strong transcriptional enhancer. This enhancer contains most, if not all of the sequence elements necessary for the T cell specific induction of the Il-2 gene by the phorbol ester TPA and the plant lectin Concanavalin A. DNase I footprinting studies with fractionated extracts obtained from induced and uninduced E14 T cells revealed numerous recognition sites for potential trans-acting factors. Five of these sites are also recognized by the TPA-activated HeLa cell factors AP-1 and AP-3. Other sites including two TATA-boxes, two purine-rich sequence motifs and two copies of the GGGPuTTTCAA motif are recognized by lymphocyte specific factors. The latter motif is highly conserved between several lymphokine genes and is therefore designated as a T cell element (TCE). In E14 T cells, pentamers of the distal TCEd confer an activity similar to that of the entire Il-2 enhancer, whereas in B and HeLa cells, the TCEd-pentamer is inactive as is the Il-2 enhancer. These data indicate the involvement of the TCEd and its recognition factor(s) in the cell type specific induction of the Il-2 gene during T cell activation.
小鼠白细胞介素2(Il-2)基因紧邻的上游区域含有一个强大的转录增强子。该增强子包含了佛波酯TPA和植物凝集素刀豆球蛋白A对Il-2基因进行T细胞特异性诱导所需的大部分(如果不是全部)序列元件。用从诱导和未诱导的E14 T细胞中获得的分级提取物进行的DNA酶I足迹研究揭示了许多潜在反式作用因子的识别位点。其中五个位点也被TPA激活的HeLa细胞因子AP-1和AP-3识别。其他位点包括两个TATA框、两个富含嘌呤的序列基序和两个GGGPuTTTCAA基序拷贝,被淋巴细胞特异性因子识别。后一个基序在几个淋巴因子基因之间高度保守,因此被指定为T细胞元件(TCE)。在E14 T细胞中,远端TCEd的五聚体赋予的活性类似于整个Il-2增强子的活性,而在B细胞和HeLa细胞中,TCEd五聚体与Il-2增强子一样无活性。这些数据表明TCEd及其识别因子参与了T细胞激活过程中Il-2基因的细胞类型特异性诱导。