Extensive DNA-binding specificity divergence of a conserved transcription regulator
Extensive DNA-binding specificity divergence of a conserved transcription regulator
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DOI：
10.1073/pnas.1019177108
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发表时间：
2011-05-03
影响因子：
11.1
通讯作者：
Johnson, Alexander D.
中科院分区：
文献类型：
--
作者：
Baker, Christopher R.;Tuch, Brian B.;Johnson, Alexander D.
转录调节因子识别的 DNA 序列可以在较长的进化距离中保持保守。例如，众所周知，酵母和哺乳动物中的许多同源调节因子可以识别相同（或密切相关）的DNA序列。与这种范式相反，我们描述了一种情况，其中转录调节因子的 DNA 结合特异性发生了如此广泛的变化（并且进化距离要小得多），以至于其顺式调节序列在不同物种中显得不相关。使用生物信息学、遗传和生化方法来记录和分析 Mat α 1（子囊菌真菌细胞类型规范的调节因子）的 DNA 结合特异性的重大变化。尽管有这种变化，Mat alpha 1 控制着半子囊菌中相同的核心基因组，因为它的 DNA 识别位点也随之进化，保留了蛋白质-DNA 相互作用，但显着改变了其分子细节。 Mat α 1 及其识别序列在 CTG 进化枝的共同祖先（白色念珠菌、卢西塔尼亚念珠菌和相关物种）中分歧最为显着，显然没有基因复制事件的帮助。我们的研究结果表明，直系同源转录调控因子之间的 DNA 结合特异性差异可能比之前想象的更为普遍，并且看似不相关的顺式调控序列可能是同源的。这些发现对于理解转录网络进化和调节回路的生物信息学分析具有重要意义。
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 cis-regulatory sequence appears unrelated in different species. Bioinformatic, genetic, and biochemical approaches were used to document and analyze a major change in the DNA-binding specificity of Mat alpha 1, a regulator of cell-type specification in ascomycete fungi. Despite this change, Mat alpha 1 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. Mat alpha 1 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 cis-regulatory sequences can nonetheless be homologous. These findings have important implications for understanding transcriptional network evolution and for the bioinformatic analysis of regulatory circuits.