Mapping Z-DNA in the human genome. Computer-aided mapping reveals a nonrandom distribution of potential Z-DNA-forming sequences in human genes.
Mapping Z-DNA in the human genome. Computer-aided mapping reveals a nonrandom distribution of potential Z-DNA-forming sequences in human genes.
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DOI：
10.1016/s0021-9258(19)49776-7
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发表时间：
1992-06
期刊：
影响因子：
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通讯作者：
G. Schroth;P. Chou;P. S. Ho
中科院分区：
文献类型：
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作者：
G. Schroth;P. Chou;P. S. Ho
在这项工作中，我们预测并绘制了超过100万个碱基对的人类DNA中潜在的Z-DNA形成序列，包含137个完整的基因。为这项研究开发的计算机程序（Z-Hunt-II）使用严格的热力学搜索策略来映射基因组序列中左手Z-DNA的出现。搜索算法已被优化，以搜索Z-DNA的潜在出现的大序列，考虑到序列类型，长度和协同性为一个给定的延伸的潜在Z-DNA形成核苷酸。在这个广泛的数据集中，我们已经确定了329个潜在的Z-DNA形成序列。数据集中潜在的Z-DNA形成序列的确切位置已经相对于基因的结构特征的位置进行了映射。该分析揭示了潜在的Z-DNA形成序列在人类基因中的明显非随机分布，最值得注意的是，强Z-DNA形成序列更常见于基因的5'端附近。我们发现35%的Z-DNA形成序列位于第一个表达外显子的上游，而只有3%的序列位于最后一个表达外显子的下游。其余62%的Z-DNA形成序列位于内含子（47.1%）或外显子（14.9%）中，也是非随机分布的，对转录起始位点附近的位置有很强的偏好。我们解释了这种分布的潜在Z-DNA形成序列向5'端的人类基因的转录诱导的超螺旋的良好建立的“双结构域模型”和这种拓扑应变在真核细胞中的Z-DNA形成的影响。
In this work, we have predicted and mapped the potential Z-DNA-forming sequences in over one million base pairs of human DNA, containing 137 complete genes. The computer program (Z-Hunt-II) developed for this study uses a rigorous thermodynamic search strategy to map the occurrence of left-handed Z-DNA in genomic sequences. The search algorithm has been optimized to search large sequences for the potential occurrence of Z-DNA, taking into account sequence type, length, and cooperativity for a given stretch of potential Z-DNA-forming nucleotides. In this extensive data set we have identified 329 potential Z-DNA-forming sequences. The exact locations of the potential Z-DNA-forming sequences in the data set have been mapped with respect to the location of structural features of the genes. This analysis reveals a distinctly nonrandom distribution of potential Z-DNA-forming sequences across human genes and, most notably, that strong Z-DNA-forming sequences are more commonly found near the 5‘ ends of genes. We find that 35% of the Z-DNA-forming sequences are located upstream of the first expressed exon, while only 3% of the sequences are located downstream of the last expressed exon. The remaining 62% of the Z-DNA-forming sequences, which are located either in introns (47.1%) or exons (14.9%), are also nonrandomly distributed, with a strong bias toward locations near the site of transcription initiation. We interpret this distribution of potential Z-DNA-forming sequences toward the 5‘ end of human genes in terms of the well established “twin-domain model” of transcription-induced supercoiling and the effect of this topological strain on Z-DNA formation in eukaryotic cells.