Frégeau C J, Bleackley R C
Department of Biochemistry, University of Alberta, Edmonton, Canada.
Nucleic Acids Res. 1991 Oct 25;19(20):5583-90. doi: 10.1093/nar/19.20.5583.
Precursor cytotoxic T lymphocytes are activated upon interaction with antigen and interleukin 2. The development of the mature killer cell phenotype is achieved by the transcription of a number of function related genes including those encoding a family of cytotoxic cell proteases (CCP). Two of these proteases, CCP1 and CCP2 encoded by C11 and B10, are shown in this report to contain cell-specific transcriptional regulatory elements within their 5'-flanking regions. Two positive regulatory sequences were mapped for C11 (-682 to -427 and -243 to -112) and one for B10 (-279 to -189). In addition each flanking region contains a region of DNA (B10 -1617 to -1049 and C11 -427 to -243) that has a negative influence on transcription. The positive regions do not appear to correspond to any previously characterized regulatory elements but do map to the same region as DNase I hypersensitive sites. When ligated to heterologous promoters these elements can still stimulate transcription but cell-specificity of expression is lost. In addition the conbination of positive regulatory region and promoter is important for the stimulatory effect. The ability of these regulatory sequences to function and to determine cell-specific transcription does not appear to be an intrinsic property but also depends upon the context.
前体细胞毒性T淋巴细胞在与抗原和白细胞介素2相互作用后被激活。成熟杀伤细胞表型的发育是通过许多功能相关基因的转录实现的，这些基因包括编码细胞毒性细胞蛋白酶（CCP）家族的基因。本报告显示，其中两种蛋白酶CCP1和CCP2分别由C11和B10编码，在其5'侧翼区域含有细胞特异性转录调控元件。为C11（-682至-427和-243至-112）定位了两个正调控序列，为B10（-279至-189）定位了一个正调控序列。此外，每个侧翼区域都包含一个对转录有负面影响的DNA区域（B10 -1617至-1049和C11 -427至-243）。这些正调控区域似乎与任何先前已鉴定的调控元件都不对应，但确实与DNase I超敏位点位于同一区域。当与异源启动子连接时，这些元件仍能刺激转录，但表达的细胞特异性丧失。此外，正调控区域和启动子的组合对刺激作用很重要。这些调控序列发挥功能并确定细胞特异性转录的能力似乎不是一种内在特性，还取决于上下文。
