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首页> 外文期刊>Molecular and Cellular Biology >Structure and tissue-specific expression of the human metallothionein IB gene.
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Structure and tissue-specific expression of the human metallothionein IB gene.

机译：人金属硫蛋白IB基因的结构和组织特异性表达。

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摘要

The human metallothionein (MT) IB gene (hMT-IB) is located in a region of human DNA containing at least four tandemly arranged MT genes. As deduced from its sequence, hMT-IB is likely to encode a functional protein. However, the predicted amino acid sequence differed from the hMT-I amino acid sequence in four positions. Most remarkable was the presence of an additional cysteine. Like other MT genes, hMT-IB has at least two copies of the metal-responsive element upstream from the transcription initiation site. These elements probably are responsible for the metal responsiveness of the hMT-IB promoter, leading to inducible expression of fused heterologous genes. Unlike the hMT-IIA and hMT-IA genes described previously, which are expressed in many different cell types, a high level of expression of the endogenous hMT-IB gene could be detected only in human hepatoma and renal carcinoma cell lines. Therefore, this is the first MT gene described which exhibits tissue specificity of expression. This specificity is controlled by a cis-acting mechanism involving methylation, since incubation of nonexpressing cells with an inhibitor of DNA methylation led to activation of the hMT-IB gene. In support of this notion, we found that the 5' flanking region of the hMT-IB gene was highly methylated in HeLa cells, a nonexpressing cell type, but it was not methylated in a hepatoma (expressing) cell line.
机译：人类金属硫蛋白（MT）IB基因（hMT-IB）位于人类DNA区域，该区域包含至少四个串联排列的MT基因。从其序列推导，hMT-IB很可能编码功能蛋白。然而，预测的氨基酸序列在四个位置与hMT-1氨基酸序列不同。最引人注目的是另外一个半胱氨酸的存在。像其他MT基因一样，hMT-IB在转录起始位点上游具有至少两个拷贝的金属反应元件。这些元件可能负责hMT-IB启动子的金属反应性，导致融合异源基因的诱导表达。与先前描述的在许多不同细胞类型中表达的hMT-IIA和hMT-IA基因不同，仅在人肝癌和肾癌细胞系中可以检测到高水平的内源性hMT-IB基因表达。因此，这是描述的第一个表现出组织表达特异性的MT基因。该特异性受涉及甲基化的顺式作用机制控制，因为将非表达细胞与DNA甲基化抑制剂一起孵育会导致hMT-IB基因的激活。为了支持该观点，我们发现hMT-IB基因的5'侧翼区域在HeLa细胞（一种非表达细胞类型）中高度甲基化，但在肝癌（表达）细胞系中并未甲基化。

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