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首页> 外文期刊>Molecular and Cellular Biology >Roles of fetal G gamma-globin promoter elements and the adult beta-globin 3' enhancer in the stage-specific expression of globin genes.
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Roles of fetal G gamma-globin promoter elements and the adult beta-globin 3' enhancer in the stage-specific expression of globin genes.

机译：胎儿Gγ球蛋白启动子元件和成人β球蛋白3'增强子在球蛋白基因的阶段特异性表达中的作用。

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The human fetal G gamma-globin and adult beta-globin genes are expressed in a tissue- and developmental stage-specific pattern in transgenic mice: the G gamma gene in embryonic cells and the beta gene in fetal and adult erythroid cells. Several of the cis-acting DNA sequences thought to be responsible for these patterns of expression are located 5' to the G gamma-globin gene and 3' to the beta-globin gene. To further define the locations and functional roles of these elements, we examined the effects of 5' truncations on the expression of the G gamma-globin gene, as well as the ability of G gamma-globin upstream sequences to alter the developmental regulation of a beta-globin gene, as well as the ability of G gamma-globin upstream sequences to alter the developmental regulation of a beta-globin gene. We found that sequences between -201 and -136 are essential for expression of the G gamma-globin gene, whereas those upstream of -201 have little effect on the level or tissue or stage specificity of G gamma-globin expression. The G gamma-globin upstream sequences from -201 to -136 were, furthermore, capable of activating a linked beta-globin gene in embryonic blood cells; however, a G gamma-globin fragment from -383 to -206 was similarly active in this assay, and the complete fragment from -383 to -136 was considerably more active than either of the smaller fragments, suggesting the presence of multiple cis-acting elements for embryonic blood cells. Our data also suggested the possibility of a negative regulatory element between -201 and -136. These results are discussed in relation to several DNA elements in the G gamma-globin upstream region, which have been shown to bind nuclear factors in erythroid cells. Finally, we observed that removal of the beta-globin 3'-flanking sequences, including the 3' enhancer, from the G gamma-globin upstream-beta-globin hybrid gene resulted in a 25-fold reduction in expression in embryonic blood cells. This suggests that the beta-globin 3' enhancer is potentially active at the embryonic stage and thus cannot be solely responsible for the fetal or adult specificity of the beta-globin gene.
机译：在转基因小鼠中，人类胎儿的Gγ珠蛋白和成年的β珠蛋白基因以组织和发育阶段特异性模式表达：胚胎细胞中的Gγ基因和胎儿和成年的类红细胞中的β基因。认为负责这些表达方式的几个顺式作用DNA序列位于Gγ-球蛋白基因的5'和β-球蛋白基因的3'。为了进一步定义这些元件的位置和功能角色，我们研究了5'截短对Gγ珠蛋白基因表达的影响，以及Gγ珠蛋白上游序列改变a的发育调控的能力。 β-珠蛋白基因，以及Gγ-珠蛋白上游序列改变β-珠蛋白基因发育调控的能力。我们发现-201和-136之间的序列对于Gγ-珠蛋白基因的表达必不可少，而-201上游的序列对Gγ-珠蛋白表达的水平或组织或阶段特异性影响很小。而且，从-201到-136的Gγ-珠蛋白上游序列能够激活胚胎血细胞中的连接的β-珠蛋白基因。但是，在此测定法中，-383至-206的Gγ珠蛋白片段具有相似的活性，并且-383至-136的完整片段比任何较小的片段都具有更高的活性，表明存在多个顺式作用胚胎血细胞的元素。我们的数据还表明，负调节元素可能在-201和-136之间。讨论了有关Gγ珠蛋白上游区域中几个DNA元素的结果，这些元素已显示与红细胞中的核因子结合。最后，我们观察到从γ-球蛋白上游-β-球蛋白杂合基因中去除β-球蛋白3'-侧翼序列，包括3'增强子，导致胚胎血细胞中表达降低25倍。这表明β-珠蛋白3'增强子在胚胎期可能具有活性，因此不能完全负责β-珠蛋白基因的胎儿或成人特异性。

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