An insulator element and condensed chromatin region separate the chicken β-globin locus from an independently regulated erythroid-specific folate receptor gene

An insulator element and condensed chromatin region separate the chicken β-globin locus from an independently regulated erythroid-specific folate receptor gene
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DOI:
10.1093/emboj/18.14.4035
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发表时间:
1999-07-15
期刊:
影响因子:
11.4
通讯作者:
Felsenfeld, G
Felsenfeld, G
中科院分区:
生物学1区
文献类型:
--
作者:
Prioleau, MN;Nony, P;Felsenfeld, G

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我们已经确定了一个叶酸受体基因上游的鸡β-珠蛋白基因座和它分开的沉默染色质的16 kbp的区域,我们发现,这种受体只表达在红细胞分化(CFU-E)的阶段之前的β-珠蛋白基因的激活,与叶酸受体在增殖中的作用一致。这一发现提出了这两个位点在红细胞生成过程中是如何调节的问题。我们的数据表明,叶酸受体基因和β-珠蛋白基因座的调控是独立的。我们发现,叶酸受体基因上游的3.3 kbp的DNA区域足以诱导CFU-E期细胞中转基因的强表达。我们还发现,β-珠蛋白基因座和叶酸受体基因之间的区域是完全甲基化和浓缩在这个阶段的分化。它的3'边界与5' β-珠蛋白绝缘体一致。我们推测,5'β-珠蛋白边界元件可能是重要的适当调节两个相邻的领域在分化过程中的两个不同阶段激活。
We have identified a folate receptor gene upstream of the chicken beta-globin locus and separated from it by a 16 kbp region of silent chromatin, We find that this receptor is expressed only at a stage of erythroid differentiation (CFU-E) preceding the activation of beta-globin genes, consistent with the role of folate receptors in proliferation. This discovery raises the question of how these two loci are regulated during erythropoiesis. Our data suggest that the folate receptor gene and the beta-globin locus are regulated independently. We show that a 3.3 kbp DNA region upstream of the folate receptor gene is sufficient to induce strong expression of a transgene in CFU-E stage cells. We also find that the region between the beta-globin locus and the folate receptor gene is fully methylated and condensed at this stage of differentiation. Its 3' boundary coincides with the 5' beta-globin insulator. We speculate that the 5' beta-globin boundary element might be important for the proper regulation of two adjacent domains activated at two different stages during differentiation.