Stein, Claudia, Bardet, Anais, Roma, Guglielmo, Bergling, Sebastian, Clay, Ieuan, Ruchti, Alexandra, Agarinis, Claudia, Schmelzle, Tobias, Bouwmeester, Antonius, Schuebeler, Dirk and Bauer, Andreas (2015) YAP1 exerts its transcriptional control via TEAD-mediated activation of enhancers. Plos Genetics.

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 nontransformed
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 normal and cancer setting.

Item Type:	Article
Keywords:	ChIP-seq; enhancer; TEAD1; transcriptional regulation; YAP1
Date Deposited:	13 Oct 2015 13:11
Last Modified:	13 Oct 2015 13:11
URI:	https://oak.novartis.com/id/eprint/26520