Klug J, Knapp S, Castro I, Beato M
Philipps-Universität Marburg, Institut für Molekularbiologie und Tumorforschung, Germany.
Mol Cell Biol. 1994 Sep;14(9):6208-18. doi: 10.1128/mcb.14.9.6208-6218.1994.
The rabbit uteroglobin gene is expressed in a variety of epithelial cell types like the lung Clara cells and the glandular and luminal epithelial cells of the endometrium. Expression in Clara cells is on a high constitutive level, whereas expression in the rabbit endometrium is under tight hormonal control. One important element of the rabbit uteroglobin gene mediating its efficient transcription in two epithelial cell lines from human endometrium (Ishikawa) and lung (NCI-H441) is its noncanonical TATA box (TACA). Here, we show that two factors (TATA core factor [TCF] and TATA palindrome factor [TPF]) different from the TATA-box binding protein bind to the DNA major groove at two adjacent sites within the uteroglobin TATA-box region and that one of them (TCF) is specifically expressed in cell lines derived from uteroglobin-expressing tissues. The binding sites for TCF and TPF, respectively, are both required for efficient transcription in Ishikawa and NCI-H441 cells. Mutation of the TACA box, which we show is a poor TATA box in functional terms, to a canonical TATA motif does not affect TCF and TPF binding. Therefore, we suggest that the function of the unusual cytosine could be to reduce rabbit uteroglobin expression in cells lacking TCF and that the interaction of TATA-box binding protein with the weak TACA site is facilitated in TCF- and TPF-positive cells.
兔子宫珠蛋白基因在多种上皮细胞类型中表达,如肺的克拉拉细胞以及子宫内膜的腺上皮细胞和腔上皮细胞。在克拉拉细胞中的表达处于高水平的组成型,而在兔子宫内膜中的表达则受到严格的激素控制。兔子宫珠蛋白基因在人子宫内膜(石川细胞系)和肺(NCI-H441细胞系)的两种上皮细胞系中介导其有效转录的一个重要元件是其非典型TATA盒(TACA)。在此,我们表明,两个不同于TATA盒结合蛋白的因子(TATA核心因子[TCF]和TATA回文因子[TPF])结合到子宫珠蛋白TATA盒区域内两个相邻位点的DNA大沟上,并且其中一个因子(TCF)在源自表达子宫珠蛋白组织的细胞系中特异性表达。TCF和TPF的结合位点对于石川细胞系和NCI-H441细胞中的有效转录都是必需的。我们发现从功能角度来看是一个较差TATA盒的TACA盒突变为典型TATA基序并不影响TCF和TPF的结合。因此,我们认为异常胞嘧啶的功能可能是在缺乏TCF的细胞中降低兔子宫珠蛋白的表达,并且在TCF和TPF阳性细胞中促进TATA盒结合蛋白与弱TACA位点的相互作用。