The coactivator p300/CREB-binding protein (CBP) regulates genes by facilitating the assembly of transcriptional machinery and by acetylating histones and other factors. However, it remains mostly unclear how both functions of p300 are dynamically coordinated during gene control. Here, we showed that p300 can orchestrate two functions through the formation of dynamic clusters with certain transcription factors (TFs), which is mediated by the interactions between a TF’s transactivation domain (TAD) and the intrinsically disordered regions of p300. Co-condensation can enable spatially defined, all-or-none activation of p300’s catalytic activity, priming the recruitment of coactivators, including Brd4. We showed that co-condensation can modulate transcriptional initiation rate and burst duration of target genes, underlying nonlinear gene regulatory functions. Such modulation is consistent with how p300 might shape gene bursting kinetics globally. Altogether, these results suggest an intriguing gene regulation mechanism, in which TF and p300 co-condensation contributes to transcriptional bursting regulation and cooperative gene control.

辅助激活剂p300 / CREB结合蛋白（CBP）通过促进转录机制的组装以及乙酰化组蛋白和其他因子来调节基因。然而，大多数尚不清楚在基因控制过程中如何动态协调p300的两个功能。在这里，我们表明p300可以通过形成具有某些转录因子（TFs）的动态簇来协调两种功能，这是由TF的反式激活域（TAD）和p300的内在无序区域之间的相互作用介导的。共聚可以使p300的催化活性在空间上定义为全激活或全激活，从而引发了包括Brd4在内的共激活剂的募集。我们发现共聚可以调节靶基因的转录起始速率和猝发持续时间，潜在的非线性基因调控功能。这种调节与p300如何在整体上塑造基因爆发动力学相一致。总而言之，这些结果表明了一种有趣的基因调控机制，其中TF和p300共缩合有助于转录猝发调控和协同基因控制。