PMID- 26258633
OWN - NLM
STAT- MEDLINE
DCOM- 20160428
LR  - 20240402
IS  - 1476-4679 (Electronic)
IS  - 1465-7392 (Print)
IS  - 1465-7392 (Linking)
VI  - 17
IP  - 9
DP  - 2015 Sep
TI  - Genome-wide association between YAP/TAZ/TEAD and AP-1 at enhancers drives 
      oncogenic growth.
PG  - 1218-27
LID - 10.1038/ncb3216 [doi]
AB  - 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.
FAU - Zanconato, Francesca
AU  - Zanconato F
AD  - Department of Molecular Medicine, University of Padua School of Medicine, viale 
      Colombo 3 35126 Padua, Italy.
FAU - Forcato, Mattia
AU  - Forcato M
AD  - Center for Genome Research, Department of Life Sciences, University of Modena and 
      Reggio Emilia, via G. Campi 287 41100 Modena, Italy.
FAU - Battilana, Giusy
AU  - Battilana G
AD  - Department of Molecular Medicine, University of Padua School of Medicine, viale 
      Colombo 3 35126 Padua, Italy.
FAU - Azzolin, Luca
AU  - Azzolin L
AD  - Department of Molecular Medicine, University of Padua School of Medicine, viale 
      Colombo 3 35126 Padua, Italy.
FAU - Quaranta, Erika
AU  - Quaranta E
AD  - Department of Molecular Medicine, University of Padua School of Medicine, viale 
      Colombo 3 35126 Padua, Italy.
FAU - Bodega, Beatrice
AU  - Bodega B
AD  - Genome Biology Unit, Istituto Nazionale di Genetica Molecolare (INGM) 'Romeo and 
      Enrica Invernizzi', via Francesco Sforza 35 Milan 20126, Italy.
FAU - Rosato, Antonio
AU  - Rosato A
AD  - Department of Surgery, Oncology and Gastroenterology, University of Padua School 
      of Medicine, Via Gattamelata 64 35126 Padua, Italy.
AD  - Istituto Oncologico Veneto IOV-IRCCS, Via Gattamelata 64 35126 Padua, Italy.
FAU - Bicciato, Silvio
AU  - Bicciato S
AD  - Center for Genome Research, Department of Life Sciences, University of Modena and 
      Reggio Emilia, via G. Campi 287 41100 Modena, Italy.
FAU - Cordenonsi, Michelangelo
AU  - Cordenonsi M
AD  - Department of Molecular Medicine, University of Padua School of Medicine, viale 
      Colombo 3 35126 Padua, Italy.
FAU - Piccolo, Stefano
AU  - Piccolo S
AD  - Department of Molecular Medicine, University of Padua School of Medicine, viale 
      Colombo 3 35126 Padua, Italy.
LA  - eng
SI  - GEO/GSE66083
GR  - 670126/ERC_/European Research Council/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150810
PL  - England
TA  - Nat Cell Biol
JT  - Nature cell biology
JID - 100890575
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (TEA Domain Transcription Factors)
RN  - 0 (TEAD1 protein, human)
RN  - 0 (Transcription Factor AP-1)
RN  - 0 (Transcription Factors)
RN  - 0 (YAP-Signaling Proteins)
RN  - 0 (YAP1 protein, human)
RN  - EC 2.3.- (Acyltransferases)
RN  - EC 2.3.1.- (TAFAZZIN protein, human)
SB  - IM
MH  - Acyltransferases
MH  - Adaptor Proteins, Signal Transducing/physiology
MH  - Animals
MH  - Carcinogenesis/genetics/metabolism
MH  - Cell Line, Tumor
MH  - DNA-Binding Proteins/physiology
MH  - *Enhancer Elements, Genetic
MH  - Female
MH  - *Gene Expression Regulation, Neoplastic
MH  - Genome-Wide Association Study
MH  - HEK293 Cells
MH  - Humans
MH  - Male
MH  - Mice, Knockout
MH  - Nuclear Proteins/physiology
MH  - Phosphoproteins/physiology
MH  - Protein Binding
MH  - Signal Transduction
MH  - Skin Neoplasms/*genetics/metabolism/pathology
MH  - TEA Domain Transcription Factors
MH  - Transcription Factor AP-1/*genetics
MH  - Transcription Factors/physiology
MH  - *Transcriptional Activation
MH  - Tumor Burden
MH  - YAP-Signaling Proteins
PMC - PMC6186417
MID - EMS79986
COIS- The authors declare no competing financial interest.
EDAT- 2015/08/11 06:00
MHDA- 2016/04/29 06:00
PMCR- 2018/10/14
CRDT- 2015/08/11 06:00
PHST- 2015/03/20 00:00 [received]
PHST- 2015/07/02 00:00 [accepted]
PHST- 2015/08/11 06:00 [entrez]
PHST- 2015/08/11 06:00 [pubmed]
PHST- 2016/04/29 06:00 [medline]
PHST- 2018/10/14 00:00 [pmc-release]
AID - ncb3216 [pii]
AID - 10.1038/ncb3216 [doi]
PST - ppublish
SO  - Nat Cell Biol. 2015 Sep;17(9):1218-27. doi: 10.1038/ncb3216. Epub 2015 Aug 10.