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

Francesca Zanconato, Mattia Forcato, Giusy Battilana, Luca Azzolin, Erika Quaranta, Beatrice Bodega, Antonio Rosato, Silvio Bicciato, Michelangelo Cordenonsi, Stefano Piccolo

Research output: Contribution to journalArticle

291 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1218-1227
Number of pages10
JournalNature Cell Biology
Volume17
Issue number9
DOIs
Publication statusPublished - Sep 1 2015

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Transcription Factor AP-1
Genome
Growth
Chromatin
Carcinogenesis
S Phase
Mitosis
Knockout Mice
Breast Neoplasms
Skin
DNA
Genes
Proteins

ASJC Scopus subject areas

  • Cell Biology

Cite this

Zanconato, F., Forcato, M., Battilana, G., Azzolin, L., Quaranta, E., Bodega, B., ... Piccolo, S. (2015). Genome-wide association between YAP/TAZ/TEAD and AP-1 at enhancers drives oncogenic growth. Nature Cell Biology, 17(9), 1218-1227. https://doi.org/10.1038/ncb3216

Genome-wide association between YAP/TAZ/TEAD and AP-1 at enhancers drives oncogenic growth. / Zanconato, Francesca; Forcato, Mattia; Battilana, Giusy; Azzolin, Luca; Quaranta, Erika; Bodega, Beatrice; Rosato, Antonio; Bicciato, Silvio; Cordenonsi, Michelangelo; Piccolo, Stefano.

In: Nature Cell Biology, Vol. 17, No. 9, 01.09.2015, p. 1218-1227.

Research output: Contribution to journalArticle

Zanconato, F, Forcato, M, Battilana, G, Azzolin, L, Quaranta, E, Bodega, B, Rosato, A, Bicciato, S, Cordenonsi, M & Piccolo, S 2015, 'Genome-wide association between YAP/TAZ/TEAD and AP-1 at enhancers drives oncogenic growth', Nature Cell Biology, vol. 17, no. 9, pp. 1218-1227. https://doi.org/10.1038/ncb3216
Zanconato F, Forcato M, Battilana G, Azzolin L, Quaranta E, Bodega B et al. Genome-wide association between YAP/TAZ/TEAD and AP-1 at enhancers drives oncogenic growth. Nature Cell Biology. 2015 Sep 1;17(9):1218-1227. https://doi.org/10.1038/ncb3216
Zanconato, Francesca ; Forcato, Mattia ; Battilana, Giusy ; Azzolin, Luca ; Quaranta, Erika ; Bodega, Beatrice ; Rosato, Antonio ; Bicciato, Silvio ; Cordenonsi, Michelangelo ; Piccolo, Stefano. / Genome-wide association between YAP/TAZ/TEAD and AP-1 at enhancers drives oncogenic growth. In: Nature Cell Biology. 2015 ; Vol. 17, No. 9. pp. 1218-1227.
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