文章基本信息

标题：The minimal promoter plays a major role in silencing of the galago γ-globin gene in adult erythropoiesis
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作者：Qiliang Li ; Xiangdong Fang ; Hemei Han 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2004
卷号：101
期号：21
页码：8096-8101
DOI：10.1073/pnas.0402594101
语种：English
出版社：The National Academy of Sciences of the United States of America
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.