title: YAP1 Exerts Its Transcriptional Control via TEAD-Mediated Activation of Enhancers.
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.
authors: Developmental and Molecular Pathways, Novartis Institutes for Biomedical Research, Novartis Pharma AG, Basel, Switzerland.
authors: Claudia
authors: C
authors: Stein
authors: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
authors: Anaïs Flore
authors: AF
authors: Bardet
authors: Developmental and Molecular Pathways, Novartis Institutes for Biomedical Research, Novartis Pharma AG, Basel, Switzerland.
authors: Guglielmo
authors: G
authors: Roma
authors: Developmental and Molecular Pathways, Novartis Institutes for Biomedical Research, Novartis Pharma AG, Basel, Switzerland.
authors: Sebastian
authors: S
authors: Bergling
authors: Developmental and Molecular Pathways, Novartis Institutes for Biomedical Research, Novartis Pharma AG, Basel, Switzerland.
authors: Ieuan
authors: I
authors: Clay
authors: Developmental and Molecular Pathways, Novartis Institutes for Biomedical Research, Novartis Pharma AG, Basel, Switzerland.
authors: Alexandra
authors: A
authors: Ruchti
authors: Developmental and Molecular Pathways, Novartis Institutes for Biomedical Research, Novartis Pharma AG, Basel, Switzerland.
authors: Claudia
authors: C
authors: Agarinis
authors: Oncology, Novartis Institutes for Biomedical Research, Novartis Pharma AG, Basel, Switzerland.
authors: Tobias
authors: T
authors: Schmelzle
authors: Developmental and Molecular Pathways, Novartis Institutes for Biomedical Research, Novartis Pharma AG, Basel, Switzerland.
authors: Tewis
authors: T
authors: Bouwmeester
authors: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland; University of Basel, Faculty of Sciences, Basel, Switzerland.
authors: Dirk
authors: D
authors: Schübeler
authors: Developmental and Molecular Pathways, Novartis Institutes for Biomedical Research, Novartis Pharma AG, Basel, Switzerland.
authors: Andreas
authors: A
authors: Bauer
mesh_terms: D000107:Acetylation; D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D001483:Base Sequence; D001665:Binding Sites; D045744:Cell Line, Tumor; D016384:Consensus Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D006657:Histones / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000502:physiology*; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D000091262:TEA Domain Transcription Factors; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D059467:Transcriptome; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D006657:Histones; D009687:Nuclear Proteins; D010750:Phosphoproteins; D000091262:TEA Domain Transcription Factors; C057182:TEAD1 protein, human; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human