Phase separation of TAZ compartmentalizes the transcription machinery to promote gene expression

Yi Lu, Tiantian Wu, Orit Gutman, Huasong Lu, Qiang Zhou, Yoav I. Henis, Kunxin Luo*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

258 Scopus citations

Abstract

TAZ promotes growth, development and tumorigenesis by regulating the expression of target genes. However, the manner in which TAZ orchestrates the transcriptional responses is poorly defined. Here we demonstrate that TAZ forms nuclear condensates through liquid–liquid phase separation to compartmentalize its DNA-binding cofactor TEAD4, coactivators BRD4 and MED1, and the transcription elongation factor CDK9 for transcription. TAZ forms phase-separated droplets in vitro and liquid-like nuclear condensates in vivo, and this ability is negatively regulated by Hippo signalling through LATS-mediated phosphorylation and is mediated by the coiled-coil (CC) domain. Deletion of the TAZ CC domain or substitution with the YAP CC domain prevents the phase separation of TAZ and its ability to induce the expression of TAZ-specific target genes. Thus, we identify a mechanism of transcriptional activation by TAZ and demonstrate that pathway-specific transcription factors also engage the phase-separation mechanism for efficient and specific transcriptional activation.

Original languageEnglish
Pages (from-to)453-464
Number of pages12
JournalNature Cell Biology
Volume22
Issue number4
DOIs
StatePublished - 1 Apr 2020

Funding

FundersFunder number
National Institutes of Health
U.S. Department of Defense
National Institute of Allergy and Infectious DiseasesR01AI041757
Medical Research and Materiel CommandW81XWH-15-1-0068
China Scholarship Council

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