Nucleated transcriptional condensates amplify gene expression.

TitleNucleated transcriptional condensates amplify gene expression.
Publication TypeJournal Article
Year of Publication2020
AuthorsWei, M-T, Chang, Y-C, Shimobayashi, SF, Shin, Y, Strom, AR, Brangwynne, CP
JournalNat Cell Biol
Volume22
Issue10
Pagination1187-1196
Date Published2020 10
ISSN1476-4679
KeywordsAnimals, Cell Nucleolus, Cytoplasm, Gene Expression Regulation, Humans, Intrinsically Disordered Proteins, Mice, Organelles, Phase Transition, RNA Polymerase II, TATA-Binding Protein Associated Factors
Abstract

<p>Membraneless organelles or condensates form through liquid-liquid phase separation, which is thought to underlie gene transcription through condensation of the large-scale nucleolus or in smaller assemblies known as transcriptional condensates. Transcriptional condensates have been hypothesized to phase separate at particular genomic loci and locally promote the biomolecular interactions underlying gene expression. However, there have been few quantitative biophysical tests of this model in living cells, and phase separation has not yet been directly linked with dynamic transcriptional outputs. Here, we apply an optogenetic approach to show that FET-family transcriptional regulators exhibit a strong tendency to phase separate within living cells, a process that can drive localized RNA transcription. We find that TAF15 has a unique charge distribution among the FET family members that enhances its interactions with the C-terminal domain of RNA polymerase II. Nascent C-terminal domain clusters at primed genomic loci lower the energetic barrier for nucleation of TAF15 condensates, which in turn further recruit RNA polymerase II to drive transcriptional output. These results suggest that positive feedback between interacting transcriptional components drives localized phase separation to amplify gene expression.</p>

DOI10.1038/s41556-020-00578-6
Alternate JournalNat Cell Biol
PubMed ID32929202
Grant ListU01 DA040601 / DA / NIDA NIH HHS / United States
/ HHMI / Howard Hughes Medical Institute / United States