Driver Mark D, Onck Patrick R
Zernike Institute for Advanced Materials, University of Groningen, Nijenborgh 4, Groningen, 9746AG, Groningen, Netherlands.
Nat Commun. 2025 Mar 31;16(1):3087. doi: 10.1038/s41467-025-58445-7.
Protein production is critically dependent on gene transcription rates, which are regulated by RNA polymerase and a large collection of different transcription factors (TFs). How these transcription factors selectively address different genes is only partially known. Recent discoveries show that the differential condensation of separate TF families through phase separation may contribute to selectivity. Here we address this by conducting phase separation studies on six TFs from three different TF families with residue-scale coarse-grained molecular dynamics simulations. Our exploration of ternary TF phase diagrams reveals four dominant sticker motifs and two orthogonal driving forces that dictate the resultant condensate morphology, pointing to sequence-dependent orthogonal molecular grammar as a generic molecular mechanism that drives selective transcriptional condensation in gene expression.
蛋白质的产生严重依赖于基因转录速率，而基因转录速率由RNA聚合酶和大量不同的转录因子（TFs）调控。这些转录因子如何选择性地作用于不同基因，目前仅部分为人所知。最近的发现表明，不同TF家族通过相分离实现的差异凝聚可能有助于实现选择性。在这里，我们通过对来自三个不同TF家族的六个TF进行残基尺度粗粒度分子动力学模拟，来研究相分离。我们对三元TF相图的探索揭示了四种主要的黏附基序和两种正交驱动力，它们决定了最终凝聚物的形态，这表明序列依赖性正交分子语法是一种驱动基因表达中选择性转录凝聚的通用分子机制。
