Penix L A, Sweetser M T, Weaver W M, Hoeffler J P, Kerppola T K, Wilson C B
Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut 06520-8064, USA.
J Biol Chem. 1996 Dec 13;271(50):31964-72. doi: 10.1074/jbc.271.50.31964.
Interferon-gamma (IFN-gamma) is produced by natural killer cells and certain subsets of T cells, but the basis for its selective expression is unknown. Within the region between -108 and -40 base pairs of the IFN-gamma promoter are two conserved and essential regulatory elements, which confer activation-specific expression in T cells. This report describes studies indicating that the most proximal of these two regulatory elements is an important determinant of its restricted expression. The proximal element is a composite site that binds members of the CREB/ATF, AP-1, and octamer families of transcription factors. Jun is essential for activation-induced transcription and binds preferably as a heterodimer with ATF-2. In contrast, CREB appears to dampen transcription from this element. The CpG dinucleotide in this element is selectively methylated in Th2 T cells and other cells that do not express IFN-gamma, and methylation markedly reduces transcription factor binding. As a target for DNA methylation and for binding of transcription factors that mediate or impede transcription, this element appears to play a central role in controlling IFN-gamma expression.
γ干扰素（IFN-γ）由自然杀伤细胞和某些T细胞亚群产生，但其选择性表达的基础尚不清楚。在IFN-γ启动子的-108至-40碱基对区域内有两个保守且必需的调控元件，它们赋予T细胞中激活特异性表达。本报告描述的研究表明，这两个调控元件中最靠近近端的元件是其限制性表达的重要决定因素。近端元件是一个复合位点，可结合CREB/ATF、AP-1和八聚体转录因子家族的成员。Jun对于激活诱导的转录至关重要，并且优选作为与ATF-2的异二聚体结合。相比之下，CREB似乎会抑制该元件的转录。该元件中的CpG二核苷酸在Th2 T细胞和其他不表达IFN-γ的细胞中被选择性甲基化，甲基化会显著降低转录因子的结合。作为DNA甲基化以及介导或阻碍转录的转录因子结合的靶点，该元件似乎在控制IFN-γ表达中起核心作用。
