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TRPS1 shapes YAP/TEAD-dependent transcription in breast cancer cells

ABSTRACT: TRPS1 shapes YAP/TEAD-dependent transcription in breast cancer cells

PROVIDER: PRJNA418840 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6300330.fastq.gz	Fastqsanger.gz
	SRR6300340.fastq.gz	Fastqsanger.gz
	SRR6300350.fastq.gz	Fastqsanger.gz
	SRR6300360_1.fastq.gz	Fastqsanger.gz
	SRR6300360_2.fastq.gz	Fastqsanger.gz

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TRPS1 shapes YAP/TEAD-dependent transcription in breast cancer cells

Project 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 <mailto:bjoern.voneyss@leibniz-fli.de>.

2018-08-09 | PXD009819 | Pride

TRPS1 shapes YAP/TEAD-dependent transcription in breast cancer cells [ChIP-seq]

Project description:TRPS1 shapes YAP/TEAD-dependent transcription in breast cancer cells [ChIP-seq]

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TRPS1 shapes YAP/TEAD-dependent transcription in breast cancer cells [4C-seq]

Project description:TRPS1 shapes YAP/TEAD-dependent transcription in breast cancer cells [4C-seq]

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TRPS1 shapes YAP/TEAD-dependent transcription in breast cancer cells [ATAC-seq]

Project description:TRPS1 shapes YAP/TEAD-dependent transcription in breast cancer cells [ATAC-seq]

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TRPS1 shapes YAP/TEAD-dependent transcription in breast cancer cells [RNA-seq]

Project description:TRPS1 shapes YAP/TEAD-dependent transcription in breast cancer cells [RNA-seq]

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TRPS1 shapes YAP/TEAD-dependent transcription in breast cancer cells [ChIP-seq]

Project description:We report the ChIP-Seq profiles for TRPS1 and TEAD1 in MCF7 and T47D cell lines, and for YAP in MCF7 cells.

2018-08-07 | GSE107013 | GEO

TRPS1 shapes YAP/TEAD-dependent transcription in breast cancer cells.

Project description:Yes-associated protein (YAP), the downstream transducer of the Hippo pathway, is a key regulator of organ size, differentiation and tumorigenesis. To uncover Hippo-independent YAP regulators, we performed a genome-wide CRISPR screen that identifies the transcriptional repressor protein Trichorhinophalangeal Syndrome 1 (TRPS1) as a potent repressor of YAP-dependent transactivation. We show that TRPS1 globally regulates YAP-dependent transcription by binding to a large set of joint genomic sites, mainly enhancers. TRPS1 represses YAP-dependent function by recruiting a spectrum of corepressor complexes to joint sites. 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 suggests that restrained YAP activity favours tumour growth. High TRPS1 activity is associated with decreased YAP activity and leads to decreased frequency of tumour-infiltrating immune cells. Our study uncovers TRPS1 as an epigenetic regulator of YAP activity in breast cancer.

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TRPS1 shapes YAP/TEAD-dependent transcription in breast cancer cells [4C-seq]

Project description:We report the 4C-Seq profile of the IGFBP3 transcriptional start site in MCF7 and MCF7 TRPS1 CRISPR KO cell lines.

2018-08-07 | GSE107022 | GEO