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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Extensive DNA-binding specificity divergence of a conserved transcription regulator
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Extensive DNA-binding specificity divergence of a conserved transcription regulator

机译:保守的转录调节剂的广泛的DNA结合特异性差异

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The DNA sequence recognized by a transcription regulator can be conserved across large evolutionary distances. For example, it is known that many homologous regulators in yeasts and mammals can recognize the same (or closely related) DNA sequences. In contrast to this paradigm, we describe a case in which the DNA-binding specificity of a transcription regulator has changed so extensively (and over a much smaller evolutionary distance) that its c/s-regulatory sequence appears unrelated in different species. Bio-informatic, genetic, and biochemical approaches were used to document and analyze a major change in the DNA-binding specificity of Mated, a regulator of cell-type specification in ascomycete fungi. Despite this change. Mated controls the same core set of genes in the hemiascomycetes because its DNA recognition site has evolved with it, preserving the protein-DNA interaction but significantly changing its molecular details. Mated and its recognition sequence diverged most dramatically in the common ancestor of the CTG-clade (Candida albicans, Candida lusitaniae, and related species), apparently without the aid of a gene duplication event. Our findings suggest that DNA-binding specificity divergence between orthologous transcription regulators may be more prevalent than previously thought and that seemingly unrelated c/s-regulatory sequences can nonetheless be homologous. These findings have important implications for understanding transcriptional network evolution and for the bioinformatic analysis of regulatory circuits.
机译:转录调节子识别的DNA序列可以在较大的进化距离内保守。例如,已知酵母和哺乳动物中的许多同源调节子可以识别相同(或密切相关)的DNA序列。与这种范例相反,我们描述了一种情况,其中转录调节子的DNA结合特异性发生了如此广泛的变化(且进化距离更小),以致其c / s调节序列在不同物种中似乎无关。生物信息学,遗传和生化方法被用来记录和分析Mate的DNA结合特异性的主要变化,Mated是子囊真菌细胞类型规范的调节剂。尽管有这种变化。交配控制了半孢子菌中相同的核心基因集,因为它的DNA识别位点已经随之进化,从而保留了蛋白质与DNA的相互作用,但显着改变了其分子细节。在CTG进化枝的共同祖先(白色念珠菌,假丝酵母​​和相关物种)的交配及其识别序列差异最大,显然没有基因复制事件的帮助。我们的发现表明直系同源转录调节因子之间的DNA结合特异性差异可能比以前认为的更为普遍,而且看似无关的c / s调控序列仍可能是同源的。这些发现对于理解转录网络的进化和调节电路的生物信息学分析具有重要意义。

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