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.

Genome-wide association between YAP/TAZ/TEAD and AP-1 at enhancers drives oncogenic growth / F. Zanconato, M. Forcato, G. Battilana, L. Azzolin, E. Quaranta, B. Bodega, A. Rosato, S. Bicciato, M. Cordenonsi, S. Piccolo. - In: NATURE CELL BIOLOGY. - ISSN 1465-7392. - 17:9(2015 Sep 01), pp. 1218-1227. [10.1038/ncb3216]

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

B. Bodega;
2015

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.
Settore BIO/11 - Biologia Molecolare
10-ago-2015
Article (author)
File in questo prodotto:
File Dimensione Formato  
Zanconato2015.pdf

accesso aperto

Tipologia: Publisher's version/PDF
Dimensione 7.5 MB
Formato Adobe PDF
7.5 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/825343
Citazioni
  • ???jsp.display-item.citation.pmc??? 439
  • Scopus 613
  • ???jsp.display-item.citation.isi??? 617
social impact