Binding site turnover produces pervasive quantitative changes in transcription factor binding between closely related Drosophila species.
Binding site turnover produces pervasive quantitative changes in transcription factor binding between closely related Drosophila species.
复制标题
结合位点转换导致密切相关的果蝇物种之间的转录因子结合发生普遍的数量变化。
DOI：
10.1371/journal.pbio.1000343
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发表时间：
2010-03-23
期刊：
影响因子：
9.8
通讯作者：
Eisen MB
中科院分区：
文献类型：
--
作者：
Bradley RK;Li XY;Trapnell C;Davidson S;Pachter L;Chu HC;Tonkin LA;Biggin MD;Eisen MB
全基因组范围内比较相关果蝇物种之间的转录因子结合，突出了序列变化如何影响动物发育的生化事件。基因表达的变化在进化中起着重要的作用，但调控进化的分子机制知之甚少。在这里，我们比较了全基因组范围内的绑定的六个转录因子，启动分割沿着前后轴在两个密切相关的物种：果蝇和果蝇yakuba的胚胎。当我们在一个物种中观察到一个因子的结合时，我们几乎总是观察到该因子与另一物种中的邻位序列的结合。然而，约束力的水平差别很大。所有六个因子的结合水平的种间差异的大小和方向是强烈相关的，这表明染色质或其他因子独立的力量在介导转录因子结合的分歧的作用。尽管如此，因子特异性结合的定量变化是常见的，我们表明，它是在很大程度上由给定因子的同源识别序列的增益和损失驱动的。我们发现只有一个弱的相关性结合变化和监管功能。这些数据提供了第一个全基因组范围的图片如何适度水平的高度形态相似的物种之间的序列差异影响系统的协调作用的转录因子在动物发育过程中，并突出了在短进化距离的转录因子结合的数量变化的主导作用。动物发育过程中细胞、组织和器官的分化是通过一个过程建立的，在这个过程中，控制细胞身份和行为的基因在特定的时间和地点被打开和关闭。这一过程在很大程度上是由一系列被称为转录因子的蛋白质精心设计的，这些转录因子与DNA中的特定序列结合，从而调节邻近基因的表达。由于转录因子在塑造生物体的形式和功能方面发挥着核心作用，它们长期以来一直被认为是表型进化的主要参与者。然而，我们对DNA的变化如何影响生命系统中转录因子的结合了解甚少。在这里，我们使用生物化学和基因组技术相结合的比较，两个密切相关的果蝇属中的果蝇种，六个转录因子的结合，帮助建立形成沿着的前-后（头到尾）轴在发展中的苍蝇的特征片段。我们发现，这些密切相关的物种之间的转录因子结合的模式是广泛保守的，与这些物种的几乎相同的发展和外观一致。然而，我们还表明，尽管这些物种之间在500万年以来积累的DNA变化-大约每10个碱基对一个差异-并没有改变这些因子结合的位置，但它们对胚胎群体中每个位点结合的因子数量产生了相当大的影响。我们可以追踪这些定量差异结合的增益和损失的短序列已知优先识别这些因素，让我们关键的洞察序列变化的影响，生物化学事件的基础动物发展。
Genome-wide comparison of transcription factor binding between related Drosophila species highlights how sequence changes affect the biochemical events that underlie animal development. Changes in gene expression play an important role in evolution, yet the molecular mechanisms underlying regulatory evolution are poorly understood. Here we compare genome-wide binding of the six transcription factors that initiate segmentation along the anterior-posterior axis in embryos of two closely related species: Drosophila melanogaster and Drosophila yakuba. Where we observe binding by a factor in one species, we almost always observe binding by that factor to the orthologous sequence in the other species. Levels of binding, however, vary considerably. The magnitude and direction of the interspecies differences in binding levels of all six factors are strongly correlated, suggesting a role for chromatin or other factor-independent forces in mediating the divergence of transcription factor binding. Nonetheless, factor-specific quantitative variation in binding is common, and we show that it is driven to a large extent by the gain and loss of cognate recognition sequences for the given factor. We find only a weak correlation between binding variation and regulatory function. These data provide the first genome-wide picture of how modest levels of sequence divergence between highly morphologically similar species affect a system of coordinately acting transcription factors during animal development, and highlight the dominant role of quantitative variation in transcription factor binding over short evolutionary distances. The differentiation of cells, tissues, and organs during animal development is established by a process in which genes that control cell identity and behavior are turned on and off at specific times and places. This process is choreographed, to a large extent, by a collection of proteins known as transcription factors that bind to specific sequences in DNA and thereby modulate the expression of neighboring genes. Because of the central role that transcription factors play in shaping organismal form and function, they have long been suggested to be major players in phenotypic evolution. However, we have a poor understanding of how changes to DNA affect transcription factor binding in living systems. Here, we use a combination of biochemical and genomic techniques to compare, between two closely related species of fruit flies in the genus Drosophila, the binding of six transcription factors that help establish the characteristic segments that form along the anterior-posterior (head to tail) axis in developing flies. We show that the patterns of transcription factor binding between these closely related species are broadly conserved, consistent with the nearly identical development and appearance of these species. However, we also show that, whereas the DNA changes that have accumulated between these species in the five million years since their divergence—roughly one difference per 10 basepairs—have not altered the locations where these factors bind, they have had a considerable effect on the amount of factor bound at each site across a population of embryos. We can trace these quantitative differences in binding to the gain and loss of the short sequences known to be preferentially recognized by these factors, giving us key insights into the effect that sequence changes have on the biochemical events that underlie animal development.
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影响因子：
64.8
作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
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影响因子：
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影响因子：
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作者：
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通讯作者：
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