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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Adaptor Proteins, Signal Transducing / physiology*
  • Base Sequence
  • Binding Sites
  • Cell Line, Tumor
  • Consensus Sequence
  • DNA-Binding Proteins / metabolism*
  • Enhancer Elements, Genetic
  • Histones / metabolism
  • Humans
  • Nuclear Proteins / metabolism*
  • Phosphoproteins / physiology*
  • Protein Binding
  • Protein Processing, Post-Translational
  • TEA Domain Transcription Factors
  • Transcription Factors / metabolism*
  • Transcriptional Activation
  • Transcriptome
  • YAP-Signaling Proteins


  • Adaptor Proteins, Signal Transducing
  • DNA-Binding Proteins
  • Histones
  • Nuclear Proteins
  • Phosphoproteins
  • TEA Domain Transcription Factors
  • TEAD1 protein, human
  • Transcription Factors
  • YAP-Signaling Proteins
  • YAP1 protein, human

Grant support

CS is a NIBR presidential postdoctoral fellow. AFB is an EMBO long-term postdoctoral fellow. Research in the DS laboratory is supported by the Novartis Research Foundation, the European Union (NoE ‘‘EpiGeneSys’’ FP7- HEALTH-2010-257082, and the ‘‘Blueprint’’ consortium FP7-282510), the European Research Council (EpiGePlas) and Swiss Initiative in Systems Biology (RTD Cell Plasticity). CS, GR, SB, IC, AR, CA, TS, TB and AB are employees of Novartis Pharmaceuticals. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.