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YAP1 Exerts Its Transcriptional Control via TEAD-Mediated Activation of Enhancers
Open accessAbstract
YAP1 is a major effector of the Hippo pathway and a well-established oncogene. Elevated YAP1 activity due to mutations in Hippo pathway components or YAP1 amplification is observed in several types of human cancers. Here we investigated its genomic binding landscape in YAP1-activated cancer cells, as well as in non-transformed cells. We demonstrate that TEAD transcription factors mediate YAP1 chromatin-binding genome-wide, further explaining their dominant role as primary mediators of YAP1-transcriptional activity. Moreover, we show that YAP1 largely exerts its transcriptional control via distal enhancers that are marked by H3K27 acetylation and that YAP1 is necessary for this chromatin mark at bound enhancers and the activity of the associated genes. This work establishes YAP1-mediated transcriptional regulation at distal enhancers and provides an expanded set of target genes resulting in a fundamental source to study YAP1 function in a normal and cancer setting.
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“ChIP-seq and deepsequencing studies in cancer and normal cells showed that several YAP-binding regions also show a consensus motif for AP-1 transcriptional factors suggesting that YAP/TEAD and AP-1 cooperatively regulate target genes representing a cross-talk between YAP and JNK signalling (74,75).”
From A Tumour-Specific Molecular Network Promotes Tumour Growth in Drosophila by Enforcing a JNK-YKI Feedforward Loop (2023) · cites this paper as [74]
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“Third, YAP/TEAD bind distal regulatory elements to regulate transcription of target genes (73-75).”
From A Tumour-Specific Molecular Network Promotes Tumour Growth in Drosophila by Enforcing a JNK-YKI Feedforward Loop (2023) · cites this paper as [74]
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“Consistently, published ChIP-seq datasets34,38,39 reveal a similar phenomenon in human cancer cell lines (Figure S7F).”
From HBO1 functions as an epigenetic barrier to hepatocyte plasticity and reprogramming during liver injury (2025) · cites this paper as [38]
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The Hippo Pathway: A Master Regulatory Network Important in Cancer
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A dual role of YAP in driving TGFβ-mediated endothelial-to-mesenchymal transition
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Myt1 and Myt1l transcription factors limit proliferation in GBM cells by repressing YAP1 expression
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Role of YAP as a Mechanosensing Molecule in Stem Cells and Stem Cell-Derived Hematopoietic Cells
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Systematic review and meta‐analysis of genomic alterations in acral melanoma
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Role of YAP1 Signaling in Biliary Development, Repair, and Disease
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YAP promotes endothelial barrier repair by repressing STAT3/VEGF signaling
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Metadata
- Authors
- Stein, C., Bardet, A. F., Roma, G., Bergling, S., Clay, I., Ruchti, A., Agarinis, C., Schmelzle, T., Bouwmeester, T., Schübeler, D., & Bauer, A.
- Affiliations
- Novartis (Switzerland) (CH)
- Friedrich Miescher Institute (CH)
- University of Basel (CH)
- Corresponding author
- Schübeler, Dirk
- Bauer, Andreas
- ORCID
- Venue
- PLOS Genetics
- Publisher
- Public Library of Science (PLoS)
- Published
- 2015-08-21
- Volume
- 11
- Issue
- 8
- Pages
- e1005465
- ISSN
- 1553-7390 (ISSN-L)
- 1553-7404
- PMC
- PMC4546604
- OpenAlex
- W1539804860
- Cited by
- 414
- References
- 98
- Citations by year
- 2026: 26 · 2025: 26 · 2024: 53 · 2023: 52 · 2022: 42 · 2021: 52 · 2020: 42 · 2019: 38 · 2018: 33 · 2017: 29 · 2016: 17 · 2015: 2
- FWCI
- 14.36
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS Genetics (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- European Commission (282510, 257082)
- SystemsX.ch
- FP7 Health (HEALTH-2010-257082, 282510)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Keywords
- YAP, TEAD transcription factors, Hippo signaling pathway, enhancer activation, distal enhancers, H3K27 acetylation, chromatin binding, transcriptional regulation, oncogenes, cancer
- MeSH terms
- YAP-Signaling Proteins, TEA Domain Transcription Factors, Acetylation, Base Sequence, Binding Sites, DNA-Binding Proteins, Enhancer Elements, Genetic, Histones, Humans, Nuclear Proteins, Phosphoproteins, Protein Binding, Protein Processing, Post-Translational, Transcription Factors, Transcriptional Activation, Consensus Sequence, Cell Line, Tumor, Adaptor Proteins, Signal Transducing, Transcriptome
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