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Nucleated transcriptional condensates amplify gene expression

Ming-Tzo Wei, Yi-Che Chang, Shunsuke F. Shimobayashi, Yongdae Shin, Clifford P. Brangwynne
doi: https://doi.org/10.1101/737387
Ming-Tzo Wei
1Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544 USA
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Yi-Che Chang
1Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544 USA
2Department of Chemistry, Princeton University, Princeton, NJ 08544, USA
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Shunsuke F. Shimobayashi
1Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544 USA
3Department of Mathematical Science and Advanced Technology, Japan Agency for Marine-Earth Science and Technology, Yokohama, 236-0001, Japan
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Yongdae Shin
1Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544 USA
4Department of Mechanical and Aerospace Engineering, Seoul National University, Seoul 08826, Korea
5Interdisciplinary Program in Bioengineering, Seoul National University, Seoul 08826, Korea
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Clifford P. Brangwynne
1Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544 USA
6Howard Hughes Medical Institute
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  • For correspondence: cbrangwy@princeton.edu
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Abstract

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.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted August 21, 2019.
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Nucleated transcriptional condensates amplify gene expression
Ming-Tzo Wei, Yi-Che Chang, Shunsuke F. Shimobayashi, Yongdae Shin, Clifford P. Brangwynne
bioRxiv 737387; doi: https://doi.org/10.1101/737387
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Nucleated transcriptional condensates amplify gene expression
Ming-Tzo Wei, Yi-Che Chang, Shunsuke F. Shimobayashi, Yongdae Shin, Clifford P. Brangwynne
bioRxiv 737387; doi: https://doi.org/10.1101/737387

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