TY - JOUR
T1 - YAP condensates are highly organized hubs
AU - Hao, Siyuan
AU - Lee, Ye Jin
AU - Benhamou Goldfajn, Nadav
AU - Flores, Eduardo
AU - Liang, Jindayi
AU - Fuehrer, Hannah
AU - Demmerle, Justin
AU - Lippincott-Schwartz, Jennifer
AU - Liu, Zhe
AU - Sukenik, Shahar
AU - Cai, Danfeng
N1 - Publisher Copyright:
© 2024 The Authors
PY - 2024/6/21
Y1 - 2024/6/21
N2 - 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.
AB - 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.
KW - Biophysics
KW - molecular interaction
KW - molecular mechanism of gene regulation
KW - properties of biomolecules
KW - protein
UR - http://www.scopus.com/inward/record.url?scp=85193209166&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85193209166&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2024.109927
DO - 10.1016/j.isci.2024.109927
M3 - Article
C2 - 38784009
AN - SCOPUS:85193209166
SN - 2589-0042
VL - 27
JO - iScience
JF - iScience
IS - 6
M1 - 109927
ER -