YAP condensates are highly organized hubs

Siyuan Hao; Ye Jin Lee; Nadav Benhamou Goldfajn; Eduardo Flores; Jindayi Liang; Hannah Fuehrer; Justin Demmerle; Jennifer Lippincott-Schwartz; Zhe Liu; Shahar Sukenik; Danfeng Cai

iScience (Jun 2024)

YAP condensates are highly organized hubs

Siyuan Hao,
Ye Jin Lee,
Nadav Benhamou Goldfajn,
Eduardo Flores,
Jindayi Liang,
Hannah Fuehrer,
Justin Demmerle,
Jennifer Lippincott-Schwartz,
Zhe Liu,
Shahar Sukenik,
Danfeng Cai

Affiliations

Siyuan Hao: Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
Ye Jin Lee: Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
Nadav Benhamou Goldfajn: Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA; Department of Biophysics, Johns Hopkins University, 3400 N. Charles St., Baltimore, MD 21218, USA
Eduardo Flores: Department of Chemistry and Chemical Biology, University of California, Merced, Merced, CA 95343, USA
Jindayi Liang: Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
Hannah Fuehrer: Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
Justin Demmerle: Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
Jennifer Lippincott-Schwartz: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA
Zhe Liu: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA
Shahar Sukenik: Department of Chemistry and Chemical Biology, University of California, Merced, Merced, CA 95343, USA
Danfeng Cai: Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA; Department of Biophysics and Biophysical Chemistry, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA; Department of Oncology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA; Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA; Corresponding author

Journal volume & issue: Vol. 27, no. 6
p. 109927

Abstract

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Summary: YAP/TEAD signaling is essential for organismal development, cell proliferation, and cancer progression. As a transcriptional coactivator, how YAP activates its downstream target genes is incompletely understood. YAP forms biomolecular condensates in response to hyperosmotic stress, concentrating transcription-related factors to activate downstream target genes. However, whether YAP forms condensates under other signals, how YAP condensates organize and function, and how YAP condensates activate transcription in general are unknown. Here, we report that endogenous YAP forms sub-micron scale condensates in response to Hippo pathway regulation and actin cytoskeletal tension. YAP condensates are stabilized by the transcription factor TEAD1, and recruit BRD4, a coactivator that is enriched at active enhancers. Using single-particle tracking, we found that YAP condensates slowed YAP diffusion within condensate boundaries, a possible mechanism for promoting YAP target search. These results reveal that YAP condensate formation is a highly regulated process that is critical for YAP/TEAD target gene expression.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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