Release of paused RNA polymerase II (Pol II) requires incorporation of the positive transcription elongation factor b (P-TEFb) into the super elongation complex (SEC), thus resulting in rapid yet synchronous transcriptional activation. However, the mechanism underlying dynamic transition of P-TEFb from inactive to active state remains unclear. Here, we found that the SEC components are able to compartmentalize and concentrate P-TEFb via liquid-liquid phase separation from the soluble inactive HEXIM1 containing the P-TEFb complex. Specifically, ENL or its intrinsically disordered region is sufficient to initiate the liquid droplet formation of SEC. AFF4 functions together with ENL in fluidizing SEC droplets. SEC droplets are fast and dynamically formed upon serum exposure and required for rapid transcriptional induction. We also found that the fusion of ENL with MLL can boost SEC phase separation. In summary, our results suggest a critical role of multivalent phase separation of SEC in controlling transcriptional pause release.

释放暂停的RNA聚合酶II（Pol II）需要将正转录延伸因子b（P-TEFb）掺入超延伸复合物（SEC）中，从而导致快速而同步的转录激活。但是，P-TEFb从非活动状态到活动状态的动态过渡所基于的机制仍然不清楚。在这里，我们发现SEC组分能够通过液相和液相分离，从含有P-TEFb复合物的可溶性非活性HEXIM1中分离和浓缩P-TEFb。具体地，ENL或其固有的无序区足以引发SEC的液滴形成。AFF4与ENL一起使SEC液滴流化。SEC液滴在暴露于血清后快速动态地形成，是快速转录诱导所必需的。我们还发现ENL与MLL的融合可以促进SEC相分离。总之，我们的结果表明SEC的多价相分离在控制转录暂停释放中起着至关重要的作用。