YAP1 Exerts Its Transcriptional Control via TEAD-Mediated Activation of Enhancers.
Fiche publication
Date publication
août 2015
Journal
PLoS genetics
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BARDET Anaïs
Tous les auteurs :
Stein C, Bardet AF, Roma G, Bergling S, Clay I, Ruchti A, Agarinis C, Schmelzle T, Bouwmeester T, Schübeler D, Bauer A
Lien Pubmed
Résumé
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.
Mots clés
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
Référence
PLoS Genet. 2015 08;11(8):e1005465