Position independence and proper developmental control of gamma-globin gene expression require both a 5' locus control region and a downstream sequence element.

Q Li; J A Stamatoyannopoulos

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Position independence and proper developmental control of gamma-globin gene expression require both a 5' locus control region and a downstream sequence element.

机译：位置独立性和γ-珠蛋白基因表达的适当发育控制既需要5'基因座控制区，又需要下游序列元件。

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We have analyzed the expression of human gamma-globin genes during development in F2 progeny of transgenic mice carrying two types of constructs. In the first type, gamma-globin genes were linked individually to large (approximately 4-kb) sequence fragments spanning locus control region (LCR) hypersensitive site 2 (HS2) or HS3. These LCR fragments contained not only the core HS elements but also extensive evolutionarily conserved flanking sequences. The second type of construct contained tandem gamma- and beta-globin genes linked to identical HS2 or HS3 fragments. We show that gamma-globin expression in transgenic mice carrying HS2 gamma or HS3 gamma constructs is highly sensitive to position effects and that such effects override the cis regulatory elements present in these constructs to produce markedly different developmental patterns of gamma-globin expression in lines carrying the same transgene. In contrast, gamma-globin expression in both HS2 gamma beta and HS3 gamma beta mice is sheltered from position effects and the developmental patterns of gamma-globin expression in lines carrying the same transgene are identical and display stage-specific regulation. The results suggest that cis regulatory sequences required for proper developmental control of fetal globin expression in the presence of an LCR element reside downstream from the gamma genes.

机译：我们已经分析了人类γ-珠蛋白基因在携带两种类型构建体的转基因小鼠的F2子代发育过程中的表达。在第一种类型中，γ珠蛋白基因分别连接到跨越基因座控制区（LCR）超敏位点2（HS2）或HS3的大（约4kb）序列片段。这些LCR片段不仅包含核心HS元件，而且包含广泛的进化保守侧翼序列。第二种类型的构建体包含与相同的HS2或HS3片段相连的串联γ-和β-珠蛋白基因。我们显示，在携带HS2γ或HS3γ构造的转基因小鼠中，γ珠蛋白的表达对位置效应高度敏感，并且这种效应优先于存在于这些构造中的顺式调控元件，从而在携带该基因的品系中产生显着不同的γ珠蛋白表达发展模式。相同的转基因。相反，HS2γβ和HS3γβ小鼠中的γ珠蛋白表达不受位置影响，并且在携带相同转基因的品系中γ珠蛋白表达的发育模式是相同的，并且显示出阶段特异性调节。结果表明，在存在LCR元件的情况下，正确发育控制胎儿珠蛋白表达所需的顺式调控序列位于伽马基因的下游。

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《Molecular and Cellular Biology》 |1994年第9期|共10页
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Q Li; J A Stamatoyannopoulos;
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中图分类细胞生物学;
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1. Sheltering of gamma-globin expression from position effects requires both an upstream locus control region and a regulatory element 3' to the A gamma-globin gene. [J] . J A Stamatoyannopoulos, C H Clegg, Q Li Molecular and Cellular Biology . 1997,第1期

机译：保护γ-珠蛋白表达不受位置效应的影响，既需要上游基因座控制区，又需要γ-珠蛋白基因的3'调控元件。
2. A 46 base pair enhancer sequence within the locus activating region is required for induced expression of the gamma-globin gene during erythroid differentiation [J] . A.W. Nienhius, B. Sorrentino, D. Bodine, Nucleic acids research . 1990,第9期

机译：在红系分化期间诱导γ-珠蛋白基因的表达需要基因座激活区域内有46个碱基对的增强子序列
3. Effect of deletion of 5'HS3 or 5'HS2 of the human β-globin locus control region on the developmental regulation of globin gene expression in β-globin locus yeast artificial chromosome transgenic mice [J] . Kenneth R. Peterson, Christopher H. Clegg, Patrick A. Navas Proceedings of the National Academy of Sciences of the United States of America . 1996,第13期

机译：人β-球蛋白基因座控制区5'HS3或5'HS2缺失对β-球蛋白基因座酵母人工染色体转基因小鼠中球蛋白基因表达发育调控的影响
4. MicroRNA Locus Expression Analysis with Phylogenetic Relationship Based on MicroRNA Control from High Throughput Sequencing Data [C] . Guo Li, Lu Zuhong 2010 4th International Conference on Bioinformatics and Biomedical Engineering . 2010

机译：基于高通量测序数据的MicroRNA控制的系统发育关系的MicroRNA基因座表达分析
5. Developmental regulation of the human beta-globin locus and the role of the O and P regions in beta-like globin gene expression. [D] . Bomhoff, Anna Louise. 2007

机译：人类β-球蛋白基因座的发育调控以及O和P区在β样球蛋白基因表达中的作用。
6. Position independence and proper developmental control of gamma-globin gene expression require both a 5 locus control region and a downstream sequence element. [O] . Q Li, J A Stamatoyannopoulos 1994

机译：位置独立性和γ-珠蛋白基因表达的适当发育控制既需要5基因座控制区又需要下游序列元件。
7. Position independence and proper developmental control of gamma-globin gene expression require both a 5' locus control region and a downstream sequence element. [O] . Li, Q, Stamatoyannopoulos, J A 1994

机译：位置独立性和γ-珠蛋白基因表达的适当发育控制既需要5'基因座控制区，又需要下游序列元件。
8. Genetic engineering with a gene encoding a soybean storage protein to identify DNA sequences to control its expression: Annual report, 1993 [R] . Beachy, R N 1993

机译：用编码大豆贮藏蛋白的基因进行基因工程鉴定DNa序列以控制其表达：年度报告，1993年

Position independence and proper developmental control of gamma-globin gene expression require both a 5' locus control region and a downstream sequence element.

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