RT Journal Article SR Electronic T1 Nucleated transcriptional condensates amplify gene expression JF bioRxiv FD Cold Spring Harbor Laboratory SP 737387 DO 10.1101/737387 A1 Ming-Tzo Wei A1 Yi-Che Chang A1 Shunsuke F. Shimobayashi A1 Yongdae Shin A1 Clifford P. Brangwynne YR 2019 UL http://biorxiv.org/content/early/2019/08/16/737387.abstract AB Liquid-liquid phase separation is thought to underly gene transcription, through the condensation of the large-scale nucleolus, or in smaller assemblies known as transcriptional hubs or condensates. However, phase separation has not yet been directly linked with transcriptional output, and our biophysical understanding of transcription dynamics is poor. Here, we utilize an optogenetic approach to control condensation of key FET-family transcriptional regulators, particularly TAF15. We show that amino acid sequence-dependent phase separation of TAF15 is enhanced significantly due to strong nuclear interactions with the C-terminal domain (CTD) of RNA Pol II. Nascent CTD clusters at primed genomic loci lower the energetic barrier for nucleation of TAF15 condensates, which in turn further recruit RNA Pol II to drive transcriptional output. These results suggest a model in which positive feedback between key transcriptional components drives intermittent dynamics of localized phase separation, to amplify gene expression.