Transcription Factors Activate Genes through the Phase-Separation Capacity of Their Activation Domains

Ann Boija, Isaac A. Klein, Benjamin R. Sabari, Alessandra Dall'Agnese, Eliot L. Coffey, Alicia V. Zamudio, Charles H. Li, Krishna Shrinivas, John C. Manteiga, Nancy M. Hannett, Brian J. Abraham, Lena K. Afeyan, Yang E. Guo, Jenna K. Rimel, Charli B. Fant, Jurian Schuijers, Tong Ihn Lee, Dylan J. Taatjes, Richard A. Young

Research output: Contribution to journalArticle

175 Scopus citations

Abstract

Gene expression is controlled by transcription factors (TFs) that consist of DNA-binding domains (DBDs) and activation domains (ADs). The DBDs have been well characterized, but little is known about the mechanisms by which ADs effect gene activation. Here, we report that diverse ADs form phase-separated condensates with the Mediator coactivator. For the OCT4 and GCN4 TFs, we show that the ability to form phase-separated droplets with Mediator in vitro and the ability to activate genes in vivo are dependent on the same amino acid residues. For the estrogen receptor (ER), a ligand-dependent activator, we show that estrogen enhances phase separation with Mediator, again linking phase separation with gene activation. These results suggest that diverse TFs can interact with Mediator through the phase-separating capacity of their ADs and that formation of condensates with Mediator is involved in gene activation.

Original languageEnglish (US)
Pages (from-to)1842-1855.e16
JournalCell
Volume175
Issue number7
DOIs
StatePublished - Dec 13 2018
Externally publishedYes

Keywords

  • activation domain
  • gene activation
  • mediator
  • phase separation
  • transcription
  • transcription factor

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Boija, A., Klein, I. A., Sabari, B. R., Dall'Agnese, A., Coffey, E. L., Zamudio, A. V., Li, C. H., Shrinivas, K., Manteiga, J. C., Hannett, N. M., Abraham, B. J., Afeyan, L. K., Guo, Y. E., Rimel, J. K., Fant, C. B., Schuijers, J., Lee, T. I., Taatjes, D. J., & Young, R. A. (2018). Transcription Factors Activate Genes through the Phase-Separation Capacity of Their Activation Domains. Cell, 175(7), 1842-1855.e16. https://doi.org/10.1016/j.cell.2018.10.042