Transcription factor GATA-5 selectively up-regulates mucin gene expression
Transcription factor GATA-5 selectively up-regulates mucin gene expression
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DOI：
10.1007/s00432-003-0537-4
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发表时间：
2004-05-01
影响因子：
3.6
通讯作者：
Yuasa, Y
中科院分区：
文献类型：
--
作者：
Ren, CY;Akiyama, Y;Yuasa, Y
目的.上皮粘蛋白、MUC 1-MUC 6和转录因子加塔-5的重叠表达模式先前已有报道。然而，人们对它们之间的功能关系知之甚少。本研究的目的是阐明粘蛋白基因的表达是否受加塔-5的调控。方法.通过质粒转染和/或腺病毒感染在COS-7和293 T细胞中瞬时过表达加塔-5。通过Western印迹分析证实了加塔-5的表达。用逆转录-PCR方法检测粘蛋白基因的表达。采用报告基因分析法分析加塔-5对粘蛋白基因启动子活性的影响。结果在COS-7和293 T细胞中，当加塔-5过表达时，MUC 2、MUC 3和MUC 4的mRNA水平增加，而MUC 1、MUC 5AC、MUC 5 B和MUC 6的mRNA水平保持不变。通过荧光素酶分析，发现加塔-5激活人MUC 2和MUC 4基因的启动子。缺乏锌指结构域的加塔-5损害了这些功能。结论.这些结果表明，加塔-5可能在调节粘蛋白表达和胃肠道上皮细胞分化中发挥重要作用。
Purpose. Overlapping expression patterns of epithelial mucins, MUC1-MUC6, and transcription factor GATA-5 were reported previously. However, the functional relationship between them is poorly understood. The aim of the current study is to elucidate whether or not expression of mucin genes is regulated by GATA-5. Methods. GATA-5 was transiently overexpressed in COS-7 and 293T cells by plasmid transfection and/or adenovirus infection. GATA-5 expression was confirmed by Western blot analysis. Expression of mucin genes was studied by reverse-transcription-PCR. Reporter gene assays were employed to analyze the effect of GATA-5 on the promoter activity of mucin genes. Results. mRNA levels of MUC2, MUC3, and MUC4 were increased, whereas those of MUC1, MUC5AC, MUC5B, and MUC6 remained unchanged upon the overexpression of GATA-5 in both COS-7 and 293T cells. By means of luciferase assay, GATA-5 was found to activate the promoters of the human MUC2 and MUC4 genes. GATA-5 lacking the zinc finger domain impaired these functions. Conclusions. These findings indicate that GATA-5 may play important roles in the regulation of mucin expression and gastrointestinal epithelial cell differentiation.