The Non-continuum Nature of Eukaryotic Transcriptional Regulation.
The Non-continuum Nature of Eukaryotic Transcriptional Regulation.
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DOI：
10.1007/5584_2021_618
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发表时间：
2022
影响因子：
--
通讯作者：
Poon GMK
中科院分区：
文献类型：
--
作者：
Poon GMK
真核生物转录因子是基因调控中具有特异性的多功能介质。这种多功能性一方面是通过上下文特异性DNA结合和身份特异性蛋白质-蛋白质伙伴关系的相互规范来实现的。这种相互作用，被称为组合控制，使得一系列复杂的转录输出在结合亲和力方面在质量上是不连接的，或非连续的。这一特征与原核基因调节因子形成鲜明对比，原核基因调节因子的活性通常随结合亲和力而定量变化。对原核模型系统的生物物理学研究和最近对转录因子的研究强调了折叠态动力学和分子水合作用在蛋白质/DNA识别中的重要作用。组合控制的分子模型分析和最近关于低亲和基因调控的文献表明，转录因子具有独特的构象动力学，这是原核dna结合蛋白无法接近或未使用的。因此，了解DNA结合和共调节因子募集的内在动力学似乎是理解转录因子如何介导真核生物基因表达的非连续结果，以及这种能力如何从古老的结构保守的对应物进化而来的关键。
Eukaryotic transcription factors are versatile mediators of specificity in gene regulation. This versatility is achieved through mutual specification by context-specific DNA binding on the one hand, and identity-specific protein-protein partnerships on the other. This interactivity, known as combinatorial control, enables a repertoire of complex transcriptional outputs that are qualitatively disjoint, or non-continuum, with respect to binding affinity. This feature contrasts starkly with prokaryotic gene regulators, whose activities in general vary quantitatively in step with binding affinity. Biophysical studies on prokaryotic model systems and more recent investigations on transcription factors highlight an important role for folded state dynamics and molecular hydration in protein/DNA recognition. Analysis of molecular models of combinatorial control and recent literature in low-affinity gene regulation suggest that transcription factors harbor unique conformational dynamics that are inaccessible or unused by prokaryotic DNA-binding proteins. Thus, understanding the intrinsic dynamics involved in DNA binding and co-regulator recruitment appears to be a key to understanding how transcription factors mediate non-continuum outcomes in eukaryotic gene expression, and how such capability might have evolved from ancient, structurally conserved counterparts.