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

Overview

Journal PLoS Genet

Specialty Genetics

Date 2015 Aug 22

PMID 26295846

Citations 234

Authors

Claudia Stein

Anais Flore Bardet

Guglielmo Roma

Sebastian Bergling

Ieuan Clay

Alexandra Ruchti

Claudia Agarinis

Tobias Schmelzle

Tewis Bouwmeester

Dirk Schubeler

Andreas Bauer

Affiliations

Soon will be listed here.

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.

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