PXD009819 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | TRPS1 shapes YAP/TEAD-dependent transcription in breast cancer cells |
Description | Yes-associated protein (YAP), the downstream transducer of the Hippo pathway is a key regulator of organ size, differentiation and tumourigenesis. Yet, the activity of YAP can also be modulated by Hippo-independent functions. To disclose these Hippo-independent regulators, we performed a genome-wide CRISPR screening approach that identified the transcriptional repressor protein Trichorhinophalangeal Syndrome 1 (TRPS1) as a potent repressor of YAP-dependent transactivation. Using RNA-Sequencing and ChIP-Sequencing approaches we show that TRPS1 globally regulates YAP-dependent transcription by binding to a large set of joint genomic sites, mainly enhancers. Mechanistically, TRPS1 represses YAP-dependent enhancers function by recruiting a spectrum of corepressor complexes to joint sites. Consequently, loss of TRPS1 leads to activation of enhancers due to increased H3K27 acetylation and an altered promoter-enhancer interaction landscape. TRPS1 is commonly amplified in breast cancer which is associated decreased YAP activity and leads to a decreased frequency of intratumoural immune cells. Consistently, depletion of TRPS1 in the syngeneic 4T1 tumour model leads to a strongly decreased tumour growth in vivo. Our study uncovers TRPS1 as a new epigenetic regulator of YAP activity and it connects repression of YAP-dependent enhancer function to breast cancer. For project-related queries, please contact bjoern.voneyss@leibniz-fli.de . |
HostingRepository | PRIDE |
AnnounceDate | 2018-08-09 |
AnnouncementXML | Submission_2018-08-09_09:47:22.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Alessandro Ori |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | biotinylated residue; monohydroxylated residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2018-05-17 23:54:39 | ID requested | |
⏵ 1 | 2018-08-09 09:47:24 | announced | |
Publication List
Elster D, Tollot M, Schlegelmilch K, Ori A, Rosenwald A, Sahai E, von Eyss B, TRPS1 shapes YAP/TEAD-dependent transcription in breast cancer cells. Nat Commun, 9(1):3115(2018) [pubmed] |
Keyword List
curator keyword: Biomedical |
submitter keyword: YAP, TAZ, Hippo, TEAD, TRPS1, Breast Cancer |
Contact List
Alessandro Ori |
contact affiliation | Leibniz Institute on Aging - Fritz Lipmann Institute |
contact email | aleori@gmail.com |
lab head | |
Alessandro Ori |
contact affiliation | EMBL |
contact email | aleori@gmail.com |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD009819
- Label: PRIDE project
- Name: TRPS1 shapes YAP/TEAD-dependent transcription in breast cancer cells