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首页> 外文期刊>Molecular and Cellular Biology >Expression of the chicken beta-globin gene cluster in mice: correct developmental expression and distributed control.
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Expression of the chicken beta-globin gene cluster in mice: correct developmental expression and distributed control.

机译：鸡β-珠蛋白基因簇在小鼠中的表达：正确的发育表达和分布控制。

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To investigate the regulation of gene clusters, we introduced the entire chicken beta-globin cluster into mice. This 35-kb region includes the four globin genes (rho-beta H-beta A-epsilon), the four upstream hypersensitive sites, and the intergenic beta A/epsilon enhancer. The chicken globins are not arranged in order of developmental expression, which is unlike the case for the human beta-globin cluster, in which gene order plays a role in the regulation of globin expression. Mice carrying the chicken cluster expressed the transgenes with the same developmental patterns as seen in the chicken. Therefore, stage-specific erythroid transcriptional milieus existed before the divergence of birds and mammals and have been conserved since then. Mice bearing the complete cluster except for a deletion removing the beta A/epsilon enhancer displayed markedly reduced expression of the beta H, beta A, and epsilon genes with efficient (but variable) rho expression. Mice carrying the four genes and beta A/epsilon enhancer but without the upstream hypersensitive sites showed reduced expression of rho, beta H, and beta A, with variable expression of epsilon. We conclude that (i) all of the genes (except possibly rho) are under the control of both the upstream hypersensitive sites and the enhancer, (ii) the influence of the control elements can extend beyond the nearest active gene, (iii) a single element (the enhancer) can influence more than one gene in a single developmental stage, (iv) the enhancer can work bidirectionally, and (v) neither the upstream sites (as a group) nor the enhancer showed developmental stage specificity. Thus, the regulation of this cluster is achieved by interaction of two distinct control regions with each of the globin genes.
机译：为了研究基因簇的调控，我们将整个鸡的β-珠蛋白簇引入小鼠体内。这个35 kb的区域包括四个球蛋白基因（rho-beta H-betaA-ε），四个上游超敏位点和基因间beta A /ε增强子。鸡球蛋白没有按照发育表达的顺序排列，这与人类β-球蛋白簇不同，后者的基因顺序在调节球蛋白表达中起作用。携带鸡群的小鼠表达的转基因具有与鸡相同的发育模式。因此，阶段特异性红系转录环境在鸟类和哺乳动物分化之前就已经存在，并且从那以后一直得到保存。携带完整簇的小鼠，除了去除βA /ε增强子的缺失外，显示具有有效（但可变）rho表达的βH，βA和ε基因的表达明显降低。携带四个基因和βA /ε增强子但没有上游超敏位点的小鼠显示rho，βH和βA的表达减少，而ε的表达却不同。我们得出的结论是：（i）所有基因（可能是rho除外）均受上游超敏位点和增强子的控制;（ii）控制元件的影响可能会延伸到最接近的活性基因之外;（iii）单个元件（增强子）可以在一个发育阶段影响一个以上的基因，（iv）增强子可以双向工作，并且（v）上游位点（作为一个整体）或增强子都没有显示出发育阶段的特异性。因此，通过两个不同的控制区与每个球蛋白基因的相互作用来实现该簇的调节。

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