Regulated expression of the human beta globin gene in transgenic mice requires an upstream globin or nonglobin promoter.
Regulated expression of the human beta globin gene in transgenic mice requires an upstream globin or nonglobin promoter.
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转基因小鼠中人β珠蛋白基因的调节表达需要上游珠蛋白或非珠蛋白启动子。
DOI：
10.1091/mbc.4.10.1077
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发表时间：
1993
影响因子：
3.3
通讯作者：
Lingrel,JB
中科院分区：
文献类型：
--
作者：
Anderson,KP;Lloyd,JA;Ponce,E;Crable,SC;Neumann,JC;Lingrel,JB
Transgenic mice have been used extensively to study elements governing the erythroid-specific developmental switch from human fetal gamma to human adult beta globin. Previous work demonstrated that a small construct composed of hypersensitive site 2 (HS2) of the locus control region (LCR) linked to the gamma and beta globin genes (HS2-gamma-beta) is sufficient for correct tissue and temporal expression of these genes, whereas HS2-beta alone is inappropriately expressed in the embryo. Two models, which are not mutually exclusive, have been proposed to explain these results and those of other constructs in transgenic mice. One model emphasizes the conserved polarity in the globin locus and suggests a distance effect whereby the beta globin gene must be removed from the LCR/HS2 to prevent an early and incorrect activation of this gene in the embryonic compartment. A second hypothesis proposes a competition between the gamma and beta globin gene promoters for interaction with the LCR/HS2. The active gamma globin gene promoter positioned between the LCR/HS2 and the beta globin gene thereby interacts with the HS2 elements early in erythroid development and is expressed until a change in putative stage-specific nuclear factors makes an interaction with the adult beta globin gene more favorable. In an effort to test the competition model, a construct has been prepared in which a small deletion was produced in the promoter region of the gamma globin gene while in the context of the HS2-gamma-beta plasmid. Analysis of this construct in transgenic mice reveals a constitutive unregulated expression of the human beta globin gene during erythroid development. To determine if this competition effect is specific for globin genes, a heterologous reporter gene has been substituted for the gamma globin gene in the construct HS2-gamma-beta. In this case, the beta globin gene exhibits correct developmental expression. This data is consistent with a model in which transcription from a promoter upstream of the beta globin gene in some manner protects this adult gene from activation by the LCR/HS2 during early development.
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影响因子：
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作者：
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影响因子：
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作者：
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DOI：
--
发表时间：
1987
期刊：
影响因子：
--
作者：
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通讯作者：
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影响因子：
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作者：
Lloyd,JA;Krakowsky,JM;Crable,SC;Lingrel,JB
通讯作者：
Lingrel,JB
影响因子：
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作者：
TALBOT, D;COLLIS, P;GREAVES, DR
通讯作者：
GREAVES, DR