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Nat Cell Biol. 2015 Sep;17(9):1218-27. doi: 10.1038/ncb3216. Epub 2015 Aug 10.

Genome-wide association between YAP/TAZ/TEAD and AP-1 at enhancers drives oncogenic growth.

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Department of Molecular Medicine, University of Padua School of Medicine, viale Colombo 3 35126 Padua, Italy.
Center for Genome Research, Department of Life Sciences, University of Modena and Reggio Emilia, via G. Campi 287 41100 Modena, Italy.
Genome Biology Unit, Istituto Nazionale di Genetica Molecolare (INGM) 'Romeo and Enrica Invernizzi', via Francesco Sforza 35 Milan 20126, Italy.
Department of Surgery, Oncology and Gastroenterology, University of Padua School of Medicine, Via Gattamelata 64 35126 Padua, Italy.
Istituto Oncologico Veneto IOV-IRCCS, Via Gattamelata 64 35126 Padua, Italy.


YAP/TAZ are nuclear effectors of the Hippo pathway regulating organ growth and tumorigenesis. Yet, their function as transcriptional regulators remains underinvestigated. By ChIP-seq analyses in breast cancer cells, we discovered that the YAP/TAZ transcriptional response is pervasively mediated by a dual element: TEAD factors, through which YAP/TAZ bind to DNA, co-occupying chromatin with activator protein-1 (AP-1, dimer of JUN and FOS proteins) at composite cis-regulatory elements harbouring both TEAD and AP-1 motifs. YAP/TAZ/TEAD and AP-1 form a complex that synergistically activates target genes directly involved in the control of S-phase entry and mitosis. This control occurs almost exclusively from distal enhancers that contact target promoters through chromatin looping. YAP/TAZ-induced oncogenic growth is strongly enhanced by gain of AP-1 and severely blunted by its loss. Conversely, AP-1-promoted skin tumorigenesis is prevented in YAP/TAZ conditional knockout mice. This work highlights a new layer of signalling integration, feeding on YAP/TAZ function at the chromatin level.

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