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PXD009819

DataSet Summary

  • HostingRepository: PRIDE
  • AnnounceDate: 2018-08-09
  • AnnouncementXML: Submission_2018-08-09_09:47:22.xml
  • DigitalObjectIdentifier:
  • ReviewLevel: Peer-reviewed dataset
  • DatasetOrigin: Original data
  • RepositorySupport: Unsupported dataset by repository
  • PrimarySubmitter: Alessandro Ori
  • 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 .
  • SpeciesList: scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
  • ModificationList: biotinylated residue; monohydroxylated residue
  • Instrument: Orbitrap Fusion Lumos

Dataset History

VersionDatetimeStatusChangeLog Entry
02018-05-17 23:54:39ID requested
12018-08-09 09:47:24announced

Publication List

  1. 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

  1. curator keyword: Biomedical
  2. 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

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  2. PRIDE project URI
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