Veitia Reiner A
Université Paris Cité, Centre National de la Recherche Scientifique (CNRS), Institut Jacques Monod, F-75006, Paris, France; Université Paris-Saclay, Institut de Biologie François Jacob, Commissariat à l'Énergie Atomique, Fontenay-aux-Roses, France.
Trends Biochem Sci. 2025 May;50(5):376-384. doi: 10.1016/j.tibs.2025.01.012. Epub 2025 Mar 5.
Transcription factors (TFs) control gene expression by binding to specific DNA motifs in cis-regulatory elements. Cooperativity has been thought to ensure TF binding specificity. Recent research suggests that, at least in yeast, the role of cooperativity has probably been overemphasized. Consequently, synergy - the collective recruitment of the transcriptional machinery by TFs bound at multiple DNA sites - emerges as a more significant mechanism for achieving the specificity of the transcriptional response. Furthermore, I argue that the concentration of TFs within phase-separated nuclear condensates and their covalent modifications play an underappreciated but crucial role in sharpening transcriptional responses through complementary mechanisms. A model integrating cooperativity, synergy, post-translational modifications, and phase separation provides a comprehensive framework to explain dynamic, context-specific transcriptional responses in eukaryotes.
转录因子（TFs）通过与顺式调控元件中的特定DNA基序结合来控制基因表达。协同作用被认为可确保转录因子结合特异性。最近的研究表明，至少在酵母中，协同作用的作用可能被过度强调了。因此，协同效应——转录因子在多个DNA位点结合时对转录机器的集体招募——成为实现转录反应特异性的一种更重要的机制。此外，我认为，相分离的核凝聚物中转录因子的浓度及其共价修饰在通过互补机制增强转录反应方面发挥了未被充分认识但至关重要的作用。一个整合了协同作用、协同效应、翻译后修饰和相分离的模型提供了一个全面的框架，以解释真核生物中动态的、上下文特异性的转录反应。
