Strain-specific variants of the mouse Cftr promoter region reveal transcriptional regulatory elements.
Strain-specific variants of the mouse Cftr promoter region reveal transcriptional regulatory elements.
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DOI：
10.1093/hmg/ddh200
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发表时间：
2004-09
影响因子：
3.5
通讯作者：
L. Ulatowski;Kirstin L Whitmore;T. Romigh;A. VanderWyden;S. Satinover;M. Drumm
中科院分区：
文献类型：
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作者：
L. Ulatowski;Kirstin L Whitmore;T. Romigh;A. VanderWyden;S. Satinover;M. Drumm
囊性纤维化跨膜传导调节因子（CFTR）mRNA水平的调控尚未完全了解。小鼠Cftr mRNA显示菌株依赖的表达差异，不能完全解释在非Cftr基因座的变化。气管和结肠表达的差异似乎主要是由于与Cftr相关的元件。在A/J、C57BL/6J和129/SvJ三个自交系之间，在翻译起始位点5 '端1.4kb范围内发现了15个单核苷酸序列变异。此外，129/SvJ相对于其他两个菌株携带100 bp缺失。通过依次缺失5 '区并测量来自胰腺管、肾集合管、唾液腺和气管的转染的小鼠上皮细胞系的荧光素酶报告子活性来研究这些变体。这些分析鉴定了C57 BL/6J启动子中的-524和-834之间的区域，但在A/J或129/SvJ中没有，其能够抑制表达。序列分析和凝胶迁移率变动分析表明，转录因子MZF参与应变依赖性效应。同样明显的是，几个报告构建体显示细胞系之间的表达差异，可能表明组织特异性元件的存在。
Regulation of cystic fibrosis transmembrane conductance regulator (CFTR) mRNA levels is not well understood. Mouse Cftr mRNA shows strain-dependent expression differences that cannot be fully explained by variation at non-Cftr loci. Differences in tracheal and colonic expression appear to be due predominantly to elements linked to Cftr. Fifteen single nucleotide sequence variations were found within 1.4 kb 5' to the translation start site between the inbred lines A/J, C57BL/6J and 129/SvJ. In addition, 129/SvJ carries a 100 bp deletion relative to the other two strains. These variants were investigated by sequentially deleting 5' regions and measuring luciferase reporter activity from transfected, mouse epithelial cell lines derived from pancreatic duct, renal collecting duct, salivary gland and trachea. These assays identified a region between -524 and -834 in the C57BL/6J promoter, but not in A/J or 129/SvJ, capable of repressing expression. Sequence analysis and gel mobility shift assays suggest that the transcription factor MZF is involved in the strain-dependent effect. It was also apparent that several reporter constructs displayed expression differences between cell lines, possibly indicating the presence of tissue-specific elements.