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Aberrant Expression Pattern of Replication-Dependent Histone H3 Subtype Genes in Human Tumor Cell Lines

机译:复制依赖性组蛋白H3亚型基因在人类肿瘤细胞系中的异常表达模式。

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摘要

We have determined the expression pattern of all 11 human replication-dependent histone H3 genes in three fetal human tissues (bladder, liver, and lung) and in eight human cell lines by RNase protection assay. In the fetal human tissues, all 11 genes were expressed to a varied extent. However, the relative contribution of each gene to the total replication-dependent histone H3 mRNA was rather similar in every tissue type. The expression pattern in the fibroblast cell line IMR 90 was similar to the expression pattern in the three fetal tissues. In contrast, the expression patterns varied substantially in seven tumor cell lines: some genes were not expressed at all, and others were expressed much less than in the fetal tissues or the fibroblast cell line. This aberrant expression was different in each of the cell lines tested. In a transient reporter gene assay using the promoters of 6 of the 11 genes, however, the relative activities of the promoters were similar in all cell lines. This indicates that the aberrant expression pattern in the different tumor cell lines is not due to a differential availability of transcription factors. We conclude that the varied expression pattern of the replication-dependent histone H3 genes in the examined human tumor cell lines is most probably due to epigenetic factors, such as the chromosomal context in the different cell lines.
机译:我们已经通过RNase保护测定确定了三种胎儿人类组织(膀胱,肝和肺)和八种人类细胞系中所有11种人类复制依赖性组蛋白H3基因的表达模式。在胎儿的人体组织中,所有11个基因均以不同程度表达。但是,在每种组织类型中,每个基因对总复制依赖性组蛋白H3 mRNA的相对贡献相当相似。成纤维细胞细胞系IMR 90中的表达模式与三个胎儿组织中的表达模式相似。相比之下,在七个肿瘤细胞系中表达模式有很大不同:一些基因根本不表达,而另一些则比胎儿组织或成纤维细胞中的表达少得多。在每个测试的细胞系中,这种异常表达是不同的。但是,在使用11个基因中的6个启动子的瞬时报告基因分析中,启动子的相对活性在所有细胞系中均相似。这表明在不同肿瘤细胞系中的异常表达模式不是由于转录因子的不同利用。我们得出结论,在所检查的人类肿瘤细胞系中复制依赖性组蛋白H3基因的变化表达模式最可能是由于表观遗传因素,例如不同细胞系中的染色体背景。

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