The human genomic melting map.
The human genomic melting map.
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DOI：
10.1371/journal.pcbi.0030093
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发表时间：
2007-05
影响因子：
4.3
通讯作者：
Hovig E
中科院分区：
文献类型：
--
作者：
Liu F;Tøstesen E;Sundet JK;Jenssen TK;Bock C;Jerstad GI;Thilly WG;Hovig E
在活细胞中，DNA的反平行双链螺旋是一种动态变化的结构。该结构涉及DNA链之间和内部的相互作用，以及构成功能性染色质的其他大分子阵列。只有通过改变DNA的构象，它才能组织和构建大量的细胞功能。特别是，DNA必须局部解螺旋或解链，并变成单链，以进行DNA复制、修复、重组和转录。先前已经表明，这种熔化协同发生，由此几个碱基对协同作用以产生熔化气泡，并且以这种方式构成相对于局部DNA单链性表现为一个单元的结构域。我们已经应用了一个完整的人类基因组，它提供了信息的倾向，形成局部气泡确定从整个序列的熔解图计算，并提出了第一份报告，其基本特征，合作的程度，以及相关性的各种物理和生物特征的人类基因组。在全球范围内，熔解图与GC含量的协变非常强烈。然而，最重要的是，DNA变性的协同性导致这种相关性在分辨率小于500 bps时较弱。这也是大多数结构和生物过程发生的分辨率水平，表明基因组解链图中固有的信息内容的重要性。http://meltmap.uio.no在活细胞中，DNA既是信息载体，又执行重要的结构任务，如组织其复制和将染色体分配给子细胞。DNA通常被描述为反平行的双链螺旋，但DNA可能被视为具有动态变化的结构。这是因为在执行大多数这些任务时，DNA螺旋必须在局部变成单链，或解开，从而在双链中产生“气泡”，就像当两股扭曲的绳子解开时发生的情况一样。在细胞中，这是借助于酶机制发生的，但也可以在实验中观察到，当温度逐渐升高时会产生气泡。我们在制作融化图时的计算是基于温度变化的，但也可以被看作是沿着基因组沿着气泡形成趋势的图。在DNA中，一个开放的气泡并不是一次打开一个碱基，而是作为一个合作事件，因为几个碱基对共同作用形成一个气泡，我们使用的算法考虑到了这一点。然后，我们探讨了熔解图和人类基因组的许多已知特征之间的相关性。我们还展示了合作的程度，并发现，融化地图携带的信息，否则无法获得。一旦解链图被计算出来，就有可能对DNA结构和功能的关系进行一些更详细的研究，以及改进用于模拟DNA与相关蛋白质在自然细胞环境中发生的算法。
In a living cell, the antiparallel double-stranded helix of DNA is a dynamically changing structure. The structure relates to interactions between and within the DNA strands, and the array of other macromolecules that constitutes functional chromatin. It is only through its changing conformations that DNA can organize and structure a large number of cellular functions. In particular, DNA must locally uncoil, or melt, and become single-stranded for DNA replication, repair, recombination, and transcription to occur. It has previously been shown that this melting occurs cooperatively, whereby several base pairs act in concert to generate melting bubbles, and in this way constitute a domain that behaves as a unit with respect to local DNA single-strandedness. We have applied a melting map calculation to the complete human genome, which provides information about the propensities of forming local bubbles determined from the whole sequence, and present a first report on its basic features, the extent of cooperativity, and correlations to various physical and biological features of the human genome. Globally, the melting map covaries very strongly with GC content. Most importantly, however, cooperativity of DNA denaturation causes this correlation to be weaker at resolutions fewer than 500 bps. This is also the resolution level at which most structural and biological processes occur, signifying the importance of the informational content inherent in the genomic melting map. The human DNA melting map may be further explored at http://meltmap.uio.no. In a living cell, DNA both is an information carrier and carries out important structural tasks, such as organizing its replication and distributing the chromosomes to the daughter cells. DNA is frequently depicted as an antiparallel double-stranded helix, but DNA may rather be viewed as having a dynamically changing structure. This is because in performing most of these tasks, it is necessary for the DNA helix to become single-stranded locally, or unwound, thereby creating “bubbles” in the double strand, much as what happens when a twisted rope with two strands is untwisted. In the cell, this happens by the aid of the enzymatic machinery, but it may also be observed in experiments when a gradual increase in temperature produces bubbles. Our calculations in producing a melting map are based on temperature changes, but may be viewed as a map of bubble formation tendencies along the genome. In DNA, an opening bubble does not open one base at a time, but rather as a cooperative event, in that several base pairs act in concert to form a bubble, and we use an algorithm that takes this aspect into consideration. We then explore the correlations between the melting map and many known features of the human genome. We also demonstrate the extent of cooperativity, and find that the melting map carries information otherwise not available. Once the melting map is calculated, a number of more detailed studies of relationships to DNA structure and function are made possible, as well as improvements of algorithms for modelling DNA with associated proteins as they occur in the natural cellular environment.
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