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首页> 外文期刊>Molecular and Cellular Biology >Replication of the Chicken β-Globin Locus: Early-Firing Origins at the 5′ HS4 Insulator and the ρ- and βA-Globin Genes Show Opposite Epigenetic Modifications
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Replication of the Chicken β-Globin Locus: Early-Firing Origins at the 5′ HS4 Insulator and the ρ- and βA-Globin Genes Show Opposite Epigenetic Modifications

机译：鸡β-球蛋白基因座的复制：在5'HS4绝缘子的早期射击起源和ρ-和βA-球蛋白基因显示相反的表观遗传修饰

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Chromatin structure is believed to exert a strong effect on replication origin function. We have studied the replication of the chicken β-globin locus, whose chromatin structure has been extensively characterized. This locus is delimited by hypersensitive sites (HSs) that mark the position of insulator elements. A stretch of condensed chromatin and another HS separate the β-globin domain from an adjacent folate receptor (FR) gene. We demonstrate here that in erythroid cells that express the FR but not the globin genes, replication initiates at four sites within the β-globin domain, one at the 5′ HS4 insulator and the other three near the ρ- and βA-globin genes. Three origins consist of G+C-rich sequences enriched in CpG dinucleotides. The fourth origin is A+T rich. Together with previous work, these data reveal that the insulator origin has unmethylated CpGs, hyperacetylated histones H3 and H4, and lysine 4-methylated histone H3. In contrast, opposite modifications are observed at the other G+C-rich origins. We also show that the whole region, including the stretch of condensed chromatin, replicates early in S phase in these cells. Therefore, different early-firing origins within the same locus may have opposite patterns of epigenetic modifications. The role of insulator elements in DNA replication is discussed.
机译：据信染色质结构对复制起点功能具有很强的作用。我们已经研究了鸡的β-珠蛋白基因座的复制，其染色质结构已得到广泛表征。该位置由标记绝缘体元件位置的超敏部位（HS）界定。一段浓缩的染色质和另一个HS将β-珠蛋白结构域与相邻的叶酸受体（FR）基因分开。我们在此证明，在表达FR但不表达球蛋白基因的类红细胞中，复制起始于β球蛋白结构域内的四个位点，一个在5'HS4绝缘子处，另一个在ρ-和β -globin基因。三个来源由富含CpG二核苷酸的富含G + C的序列组成。第四个来源是丰富的A + T。与以前的工作一起，这些数据表明绝缘子起源具有未甲基化的CpG，超乙酰化的组蛋白H3和H4和赖氨酸4甲基化的组蛋白H3。相反，在其他富含G + C的来源观察到相反的修饰。我们还显示，整个区域，包括浓缩的染色质延伸，在这些细胞的S期早期复制。因此，在同一基因座内不同的早生起源可能具有相反的表观遗传修饰模式。讨论了绝缘子在DNA复制中的作用。

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