首页> 外文期刊>Journal of Molecular Biology >The 5'HS4 core element of the human beta-globin locus control region is required for high-level globin gene expression in definitive but not in primitive erythropoiesis.
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The 5'HS4 core element of the human beta-globin locus control region is required for high-level globin gene expression in definitive but not in primitive erythropoiesis.

机译:人类β-球蛋白基因座控制区的5'HS4核心元件是确定性而非原始红细胞生成中高水平球蛋白基因表达所必需的。

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摘要

To assess the contribution of DNase I-hypersensitive site 4 (HS4) of the beta-globin locus control region (LCR) to overall LCR function we deleted a 280 bp fragment encompassing the core element of 5'HS4 from a 248 kb beta-globin locus yeast artificial chromosome (beta-YAC) and analyzed globin gene expression during development in beta-YAC transgenic mice. Four transgenic lines were established; each contained at least one intact copy of the beta-globin locus. The deletion of the 5'HS4 core element had no effect on globin gene expression during embryonic erythropoiesis. In contrast, deletion of the 5'HS4 core resulted in a significant decrease of gamma and beta-globin gene expression during definitive erythropoiesis in the fetal liver and a decrease of beta-globin gene expression in adult blood. We conclude that the core element of 5'HS4 is required for globin gene expression only in definitive erythropoiesis. Absence of the core element of HS4 may limit the ability of the LCR to provide an open chromatin domain and/or enhance gamma and beta-globin gene expression in the adult erythroid cells.
机译:为了评估β-珠蛋白基因座控制区(LCR)的DNase I超敏感位点4(HS4)对总体LCR功能的贡献,我们从248 kbβ-珠蛋白中删除了一个包含5'HS4核心元件的280 bp片段位酵母人工染色体(beta-YAC),并在beta-YAC转基因小鼠发育过程中分析了球蛋白基因表达。建立了四个转基因品系。每个都包含至少一个完整副本的β-珠蛋白基因座。 5'HS4核心元素的删除对胚胎红细胞生成过程中的球蛋白基因表达没有影响。相反,在胎儿肝的确定性红细胞生成过程中,5'HS4核心的缺失导致γ和β-珠蛋白基因表达显着下降,而成人血液中β-珠蛋白基因表达下降。我们得出结论,仅在确定的红细胞生成中,球蛋白基因表达才需要5'HS4的核心元件。 HS4核心元件的缺乏可能会限制LCR在成年红系细胞中提供开放的染色质结构域和/或增强γ和β-珠蛋白基因表达的能力。

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