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人类β-珠蛋白基因座中DNA弯曲位点的保守性和周期性

Conservation and periodicity of DNA bend sites in the human beta-globin gene locus.

作者信息

Wada-Kiyama Y, Kiyama R

机构信息

Department of Physiology, Nippon Medical School, Tokyo, Japan.

出版信息

J Biol Chem. 1995 May 26;270(21):12439-45. doi: 10.1074/jbc.270.21.12439.

DOI:10.1074/jbc.270.21.12439
PMID:7759485
Abstract

A total of seven DNA bend sites were mapped in the 4.4-kilobase human beta-globin gene region by the circular permutation assay. The periodicity of these sites (except one) was about every 700 (average 685.5 +/- 267.7) base pairs. All of the sites contained the sequence feature of short poly(dA) tracts, which are typical of DNA bending. The relative positions of the sites to the cap site were identical to those in the epsilon-globin gene region, suggesting that the bend sites were conserved during molecular evolution of the two globin genes. To explain this periodicity and conservation of the sites within the evolutionary unstable noncoding regions, we focused upon the appearance of a potential bend core sequence, A2N8A2N8A2 (A/A/A), and its complement, T2N8T2N8T2 (T/T/T). These sequences appeared in or very close to most of the bend sites of the globin gene regions, whereas other A+T-rich sequences or candidates for DNA bending did not. The distances between any two of the core sequences in the entire beta-globin locus showed a strong bias to a length of about 700 base pairs and its multiples, suggesting that the periodicity exists throughout the locus. The data presented here strengthen the idea of sequence-directed nucleosome phasing.

摘要

通过环形置换分析,在4.4千碱基的人类β-珠蛋白基因区域共定位了7个DNA弯曲位点。这些位点(除一个外)的周期性约为每700(平均685.5±267.7)个碱基对。所有位点都含有短聚(dA)序列的特征,这是DNA弯曲的典型特征。这些位点相对于帽位点的相对位置与ε-珠蛋白基因区域中的相同,表明在两个珠蛋白基因的分子进化过程中弯曲位点是保守的。为了解释进化不稳定的非编码区域内这些位点的周期性和保守性,我们关注潜在弯曲核心序列A2N8A2N8A2(A/A/A)及其互补序列T2N8T2N8T2(T/T/T)的出现。这些序列出现在珠蛋白基因区域的大多数弯曲位点内或非常接近这些位点,而其他富含A+T的序列或DNA弯曲候选序列则没有。整个β-珠蛋白基因座中任意两个核心序列之间的距离强烈偏向于约700个碱基对及其倍数的长度,表明整个基因座都存在周期性。此处给出的数据强化了序列导向核小体相位的观点。

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