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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >The minimal promoter plays a major role in silencing of the galago gamma-globin gene in adult erythropoiesis.
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The minimal promoter plays a major role in silencing of the galago gamma-globin gene in adult erythropoiesis.

机译:最小启动子在成年红细胞生成中加拉戈γ-珠蛋白基因的沉默中起主要作用。

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摘要

The human gamma-globin gene and its orthologous galago gamma-globin gene evolved from an ancestral epsilon-globin gene. In galago, expression of the gamma-gene remained restricted to the embryonic stage of development, whereas in humans, expression of the gamma-gene was recruited to the fetal stage. To localize the cis-elements responsible for this developmentally distinct regulation, we studied the expression patterns of the human gamma-gene driven by either the human or the galago gamma-promoters in transgenic mice. gamma-gene transcription driven by either promoter reached similar levels in embryonic erythropoiesis. In adult erythropoiesis the gamma-gene was silenced when controlled by the galago gamma-promoter, but it was expressed at a high level when it was linked to the human gamma-promoter. By a series of gamma-promoter truncations the sequences required for the down-regulation of the galago gamma-globin gene were localized to the minimal promoter. Furthermore, by interchanging the TATA, CCAAT,and CACCC elements between the human and galago minimal promoters we found that whereas each box made a developmentally distinctive contribution to gamma-globin gene expression, the CACCC box was largely responsible for the down-regulation of the gamma-gene in adult erythropoiesis.
机译:人γ-珠蛋白基因及其直系同源galagoγ-珠蛋白基因是从祖先ε-珠蛋白基因进化而来的。在加拉戈,伽马基因的表达仍然局限于胚胎的发育阶段,而在人类中,伽马基因的表达被募集到胎儿阶段。为了定位负责这种发育上不同的调控的顺式元件,我们研究了由人类或galagoγ-启动子驱动的人类γ基因在转基因小鼠中的表达模式。由任一启动子驱动的γ基因转录在胚胎红细胞生成中达到相似的水平。在成年的红细胞生成中,当由加拉戈伽玛启动子控制时,伽马基因被沉默,但是当它与人类伽玛启动子连接时,其高水平表达。通过一系列的γ-启动子截短,将加拉戈γ-珠蛋白基因的下调所需的序列定位于最小启动子。此外,通过在人类和加拉哥的最小启动子之间交换TATA,CCAAT和CACCC元件,我们发现,尽管每个框对γ-珠蛋白基因表达都具有发展上的独特贡献,但CACCC框在很大程度上负责了成人红细胞生成中的γ基因。

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