PXD009819

PXD009819 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2018-05-17 23:54:39	ID requested
⏵ 1	2018-08-09 09:47:24	announced

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]

curator keyword: Biomedical

submitter keyword: YAP, TAZ, Hippo, TEAD, TRPS1, Breast Cancer

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

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PRIDE project URI

• PRIDE
  1. PXD009819
     1. Label: PRIDE project
     2. Name: TRPS1 shapes YAP/TEAD-dependent transcription in breast cancer cells