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PLoS Genet. 2015 Aug 21;11(8):e1005465. doi: 10.1371/journal.pgen.1005465. eCollection 2015 Aug.

YAP1 Exerts Its Transcriptional Control via TEAD-Mediated Activation of Enhancers.

Author information

1
Developmental and Molecular Pathways, Novartis Institutes for Biomedical Research, Novartis Pharma AG, Basel, Switzerland.
2
Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
3
Oncology, Novartis Institutes for Biomedical Research, Novartis Pharma AG, Basel, Switzerland.
4
Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland; University of Basel, Faculty of Sciences, Basel, Switzerland.

Abstract

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.

PMID:
26295846
PMCID:
PMC4546604
DOI:
10.1371/journal.pgen.1005465
[Indexed for MEDLINE]
Free PMC Article

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