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TRPS1 shapes YAP/TEAD-dependent transcription in breast cancer cells
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 Trichorhinoph...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6079100/ https://www.ncbi.nlm.nih.gov/pubmed/30082728 http://dx.doi.org/10.1038/s41467-018-05370-7 |
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author | Elster, Dana Tollot, Marie Schlegelmilch, Karin Ori, Alessandro Rosenwald, Andreas Sahai, Erik von Eyss, Björn |
author_facet | Elster, Dana Tollot, Marie Schlegelmilch, Karin Ori, Alessandro Rosenwald, Andreas Sahai, Erik von Eyss, Björn |
author_sort | Elster, Dana |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-6079100 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-60791002018-08-08 TRPS1 shapes YAP/TEAD-dependent transcription in breast cancer cells Elster, Dana Tollot, Marie Schlegelmilch, Karin Ori, Alessandro Rosenwald, Andreas Sahai, Erik von Eyss, Björn Nat Commun Article 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. Nature Publishing Group UK 2018-08-06 /pmc/articles/PMC6079100/ /pubmed/30082728 http://dx.doi.org/10.1038/s41467-018-05370-7 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Elster, Dana Tollot, Marie Schlegelmilch, Karin Ori, Alessandro Rosenwald, Andreas Sahai, Erik von Eyss, Björn TRPS1 shapes YAP/TEAD-dependent transcription in breast cancer cells |
title | TRPS1 shapes YAP/TEAD-dependent transcription in breast cancer cells |
title_full | TRPS1 shapes YAP/TEAD-dependent transcription in breast cancer cells |
title_fullStr | TRPS1 shapes YAP/TEAD-dependent transcription in breast cancer cells |
title_full_unstemmed | TRPS1 shapes YAP/TEAD-dependent transcription in breast cancer cells |
title_short | TRPS1 shapes YAP/TEAD-dependent transcription in breast cancer cells |
title_sort | trps1 shapes yap/tead-dependent transcription in breast cancer cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6079100/ https://www.ncbi.nlm.nih.gov/pubmed/30082728 http://dx.doi.org/10.1038/s41467-018-05370-7 |
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