Li-Weber M, Davydov I V, Krafft H, Krammer P H
Tumor Immunology Program, German Cancer Research Center, Heidelberg.
J Immunol. 1994 Nov 1;153(9):4122-33.
Activity of the IL-4 promoter was shown to be regulated by multiple cis-acting elements. In this study, two additional regulatory elements, a CCAAT element and a 15-nucleotide element homologous to the IFN- and virus-stimulation response element (ISRE), were identified in the human promoter region at -195 to -172. The ISRE-homologous sequence was shown to interact with two nuclear proteins, IRF-2, a transcriptional repressor of the IFN genes, and an NF-1-like factor. Mutations of the ISRE site increased overall IL-4 promoter activity twofold, suggesting a possible negative role of IRF-2 in the regulation of IL-4 transcription. The CCAAT element was found to interact with NF-Y, a nuclear factor essential for expression of MHC class II genes. Mutations of the CCAAT element at -195 to -172 resulted in a substantial decrease of IL-4 promoter activity. Furthermore, NF-Y was also found to bind to the previously described NF-ATp binding site of the IL-4 promoter (-79 to -62, originally described as "P element"), and the previously described P-binding complex NF-P was shown to contain NF-Y. These findings suggest that NF-Y may play an important role in the regulation of IL-4 gene expression.
IL-4启动子的活性被证明受多个顺式作用元件调控。在本研究中，在人启动子区域-195至-172处鉴定出另外两个调控元件，一个CCAAT元件和一个与IFN-和病毒刺激反应元件（ISRE）同源的15核苷酸元件。ISRE同源序列被证明可与两种核蛋白相互作用，即IFN基因的转录抑制因子IRF-2和一种NF-1样因子。ISRE位点的突变使IL-4启动子的总体活性增加了两倍，提示IRF-2在IL-4转录调控中可能起负性作用。发现CCAAT元件可与NF-Y相互作用，NF-Y是MHC II类基因表达所必需的一种核因子。-195至-172处CCAAT元件的突变导致IL-4启动子活性大幅下降。此外，还发现NF-Y也可结合到IL-4启动子先前描述的NF-ATp结合位点（-79至-62，最初称为“P元件”），并且先前描述的P结合复合物NF-P被证明含有NF-Y。这些发现提示NF-Y可能在IL-4基因表达调控中起重要作用。
