Fig. 4
From: Liquid–liquid phase separation in human health and diseases
The function of LLPS in regulating gene transcription. a Phosphorylation regulates the transformation of initiation condensates to elongation condensates. In transcriptional initiation, RNA polymerase II (Pol II) phase-separates various factors with IDRs, such as transcription factors and coactivators, to form initiation condensates. After the transcription initiation, Pol II does not directly enter the elongation phase but pauses in a region approximately 50 bp downstream of the transcription start site, which is called promoter-proximal pausing. Thereafter, PTEFb can phase-separate into the initiation condensates through the multivalent interactions between the histidine-rich domain and carboxy-terminal domain (CTD) of Pol II. Therefore, CDK9, a subunit domain of PTEFb, can phosphorylate the negative elongation factor (NELF) and CTD. Phosphorylated NELF cannot stabilize paused Pol II and phosphorylated Pol II forms elongation condensates by hyperphosphorylated CTD, thereby achieving transcription elongation. b The transcriptional condensates can also be formed at a super-enhancer. Besides, the local RNA concentration can negatively regulate the formation of super-enhancer condensates. Low levels of RNA at regulatory DNA elements promote the formation of transcriptional condensates, whereas high levels of RNA from gene transcription can dissolve the transcriptional condensates
