GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE125606 Query DataSets for GSE125606
Status Public on Jul 16, 2019
Title A non-canonical role of YAP/TEAD is required for activation of estrogen-regulated enhancers in breast cancer [RNA-seq]
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Estrogen and estrogen receptor alpha (ERα) signaling plays an essential role in ERα-positive breast cancer. ERα mainly occupies on distal enhancers within genome and requires the cooperation of additional co-factors to tune the enhancer activity. Through in vivo proximity-dependent labeling technique BioID, we identified YAP1 and TEAD4 protein as novel co-regulators of ERα. YAP and TEAD are nuclear effectors of the Hippo pathway regulating cell proliferation, organ size and tumorigenesis. Their non-canonical function as transcriptional co-regulators for other signals have been reported but remains under investigated. Our ChIP-seq data in both MCF7 and T47D breast cancer cell lines indicated that YAP1 and TEAD4 co-bind to the strongest estrogen-responsive ERα-bound enhancers, and their bindings are augmented upon E2 stimulation. Knockdown of YAP1 or TEAD4 showed a global effect on the induction of E2/ERα target genes as examined by RNA-seq, also on E2-induced oncogenic growth of ER-positive breast cancer cells. We used Global Run-on sequencing (GRO-seq) assays to test the expression of enhancer non-coding RNAs (eRNAs), which are sensitive markers for estrogen-induced enhancer activation. Our results supported our hypothesis that the recruitment YAP/TEAD to ERα-bound enhancers is required for enhancer activation. Further studies revealed that the binding of YAP1 on ERα enhancers is a prerequisite for the recruitment of the enhancer activation machinery component MED1. These findings indicate that ERα collaborates with YAP1 and TEAD4 to activate or maintain its enhancer activity. Our data reveals a non-canonical function of YAP1 and TEAD4, which is independent of their canonical target genes, in regulating cancer growth, highlighting the potential of YAP1 and TEAD4 as actionable drug targets for ERα-positive breast cancer.
Overall design Total RNA extraction followed by high-throughput sequencing (RNA-seq).
Contributor(s) Zhao Z, Chi Z, Zhijie L
Citation(s) 31303470
Submission date Jan 24, 2019
Last update date Jul 16, 2019
Contact name Zhijie Jason Liu
Organization name Universality of Texas Health Science Center at San Antonio
Department Department of Molecular Medicine
Lab Liu lab
Street address 7703 Floyd Curl Drive
City San Antonio
State/province TEXAS
ZIP/Postal code 78229
Country USA
Platforms (1)
GPL21290 Illumina HiSeq 3000 (Homo sapiens)
Samples (12)
GSM3578129 shCtrl Veh replicate1
GSM3578130 shCtrl Veh replicate2
GSM3578131 shCtrl E2 replicate1
This SubSeries is part of SuperSeries:
GSE125609 A non-canonical role of YAP/TEAD is required for activation of estrogen-regulated enhancers in breast cancer
BioProject PRJNA516911
SRA SRP181909

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE125606_readCounts.txt.gz 447.9 Kb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap