Differential expression of the human ST5 gene in HeLa-fibroblast hybrid cell lines mediated by YY1 evidence that YY1: Plays a part in tumor suppression
Differential expression of the human ST5 gene in HeLa-fibroblast hybrid cell lines mediated by YY1 evidence that YY1: Plays a part in tumor suppression
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DOI：
10.1093/nar/24.23.4700
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发表时间：
1996-12-01
影响因子：
14.9
通讯作者：
Tsai, MM
中科院分区：
文献类型：
--
作者：
Lichy, JH;Majidi, M;Tsai, MM
通过对差异调节增强子的突变分析，我们提出了支持转录因子YY 1在HeLa/成纤维细胞体细胞杂交中的肿瘤抑制作用的证据。先前显示人ST 5基因表达为三种RNA种类，长度为4.6、3.1和2.8 kb，而两种较大的种类在所有检测的细胞系中以相似的水平表达，该2.8kb mRNA在非致瘤性杂交体中特异性表达，在本研究中，研究了该mRNA种类差异表达的基础，显示该信息来源于位于ST 5基因内含子内的启动子，细胞类型特异性表达需要位于起始位点上游1500 nt附近的增强子，该增强子的突变分析揭示了完整增强子活性所必需的一个AP 1位点和五个YY 1位点。发现YY 1 DNA结合活性水平在非致瘤细胞中比致瘤细胞高6倍，而AP 1活性在两种细胞类型中相似，这些结果表明，靶向YY 1的信号通路可能在HeLa成纤维细胞杂交瘤抑制中发挥重要作用。
Through a mutational analysis of a differentially regulated enhancer, we present evidence that supports a role for the transcription factor YY1 in tumor suppression in HeLa/fibroblast somatic cell hybrids, The human ST5 gene was previously shown to be expressed as three RNA species, 4.6, 3.1 and 2.8 kb in length, Whereas the two larger species are expressed at similar levels in all cell lines examined, the 2.8 kb mRNA is expressed specifically in non-tumorigenic hybrids, In this study, the basis for the differential expression of this mRNA species was investigated, The message was shown to originate from a promoter located within an intron of the ST5 gene, An enhancer located similar to 1500 nt upstream of the start site was required for cell type specific expression, Mutational analysis of this enhancer revealed an AP1 site and five YY1 sites which were necessary for full enhancer activity, Levels of YY1 DNA binding activity were found to be as much as 6-fold higher in the non-tumorigenic cells relative to the tumorigenic cells, while AP1 activity was similar in both cell types, These results suggest that a signaling pathway targeting YY1 may play an important role in tumor suppression in HeLa-fibroblast hybrids.