Expression profiles frame the promoter specificity dilemma of the ETS family of transcription factors
Expression profiles frame the promoter specificity dilemma of the ETS family of transcription factors
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DOI：
10.1093/nar/gkh906
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发表时间：
2004-01-01
影响因子：
14.9
通讯作者：
Graves, BJ
中科院分区：
文献类型：
--
作者：
Hollenhorst, PC;Jones, DA;Graves, BJ
作为转录因子的序列特异性DNA结合蛋白通常由基因家族编码。这些蛋白质表现出高度保守的DNA结合特性，但有望保持启动子的选择性。在这份报告中，我们使用ETS基因家族来研究这个问题，ETS基因家族是一组后生动物基因，其成员调节细胞的生长和分化，并在人类癌症中发生突变。我们测试了信使核糖核酸水平是否可以作为特异性决定因素。在23个组织和细胞系中检测了27个类似的人类ETS基因的mRNA水平。实时逆转录聚合酶链式反应提供了精确的每种基因的绝对信使核糖核酸水平的测量，精确到每个细胞一个拷贝。令人惊讶的是，每个细胞样本中至少有16个Parparog基因表达，超过一半的基因普遍表达。组织和互补细胞系表现出相似的表达模式，表明组织复杂性不是限制。每种细胞类型都没有唯一的、高表达的基因。相反，在所有样本中，仅有的8个ETS基因中有一个显示出最高的表达。DNA结合研究说明了普遍存在的ETS蛋白的重叠和独特的特异性。这些发现建立了ETS转录因子家族中启动子特异性困境的参数。
Sequence-specific DNA binding proteins that function as transcription factors are frequently encoded by gene families. Such proteins display highly conserved DNA binding properties, yet are expected to retain promoter selectivity. In this report we investigate this problem using the ets gene family, a group of metazoan genes whose members regulate cell growth and differentiation and are mutated in human cancers. We tested whether the level of mRNA can serve as a specificity determinant. The mRNA levels of the 27 paralogous human ets genes were measured in 23 tissues and cell lines. Real-time RT-PCR provided accurate measurement of absolute mRNA levels for each gene down to one copy per cell. Surprisingly, at least 16 paralogs were expressed in each cell sample and over half were expressed ubiquitously. Tissues and complementary cell lines showed similar expression patterns, indicating that tissue complexity was not a limitation. There was no unique, highly expressed gene for each cell type. Instead, one of only eight ets genes showed the highest expression in all samples. DNA binding studies illustrate both overlapping and unique specificities for ubiquitous ETS proteins. These findings establish the parameters of the promoter specificity dilemma within the ets family of transcription factors.