Abstract:<\/p>\n
YAP\/TEAD are nuclear effectors of the Hippo pathway, regulating organ size and tumorigenesis largely through promoter-associated function. However, their function as enhancer regulators remains poorly understood. Through an in vivo proximity-dependent labeling (BioID) technique, we identified YAP1 and TEAD4 protein as co-regulators of ER\u03b1 on enhancers. The binding of YAP1\/TEAD4 to ER\u03b1-bound enhancers is augmented upon E2 stimulation and is required for the induction of E2\/ER\u03b1 target genes and E2-induced oncogenic cell growth. Furthermore, their enhancer binding is a prerequisite for enhancer activation marked by eRNA transcription and for the recruitment of the enhancer activation machinery component MED1. The binding of TEAD4 on active ERE-containing enhancers is independent of its DNA-binding behavior, and instead, occurs through protein-tethering trans-binding. Our data reveal a non-canonical function of YAP1 and TEAD4 as ER\u03b1 cofactors in regulating cancer growth, highlighting the potential of YAP\/TEAD as possible actionable drug targets for ER\u03b1+ breast cancer.<\/p>\n
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Chi Zhu, Li Li, Zhao Zhang, Mingjun Bi, Karen Hernandez, Wenyue Su, Junqiang Chen, Tim Hui-Ming Huang<\/strong>, Lizhen Chen, and Zhijie Liu<\/strong>. A non-canonical role of YAP\/TEAD is required for activation of estrogen-regulated enhancers in breast cancer. Molecular Cell. 2019 Aug 22;75(4):791-806. PMID: 31303470 (*lead author)<\/p>\n <\/p>\n","protected":false},"excerpt":{"rendered":" Abstract: YAP\/TEAD are nuclear effectors of the Hippo pathway, regulating organ size and tumorigenesis largely through promoter-associated function. However, their function as enhancer regulators remains poorly understood. Through an in vivo proximity-dependent labeling (BioID) technique, we identified YAP1 and TEAD4 protein as co-regulators of ER\u03b1 on enhancers. The binding of YAP1\/TEAD4 to ER\u03b1-bound enhancers is […]<\/p>\n","protected":false},"author":264,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[3,14],"class_list":["post-1174","post","type-post","status-publish","format-standard","hentry","category-highimpactpublication","category-news"],"yoast_head":"\n