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pubmed, google, scholar, cas, cell, cells, control, data, supplementary, central, yaptaz, tead, biological, replicates, nature, yap, mdamb, information, cancer, growth, fosl, chromatin, taz, binding, peaks, transfected, yaptaztead, jun, experiments, sirnas, dna, expression, representative, shown, table, article, chipseq, target, genome, promoter, experiment, hippo, transcriptional, skin, access, signaling, biol, chipqpcr, points, xlsx,

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nature portfolio permissions reprints β-catenin-driven cancers require privacy policy downstream yap/taz/tead-occupied enhancer author information authors cancer research advertising genome research yap/taz-induced oncogenic growth yap/taz/tead peaks close yap/taz/tead peaks localized social media yap/taz/tead targets ctgf yap/taz/tead binding sites nature 503 nature 489 nature 474 nature 407 nature yap/taz/tead-bound promoters yaps94a-transduced mda-mb-231 cells verify tamoxifen-induced recombination tead4-depleted mda-mb-231 cells established yap/taz signatures tead-binding deficient yaps94a k14–cre–ert2 transgenics skin tumor development mda teton jun-dn empower tgfβ-induced metastasis yap fl/fl mice tazs89a-overexpressing mii cells yap/taz-regulated genes fra-1/ap-1 induces emt yap/taz binding profiles yap/taz-depleted cells yap/taz/tead peaks 40841 disturbs yap1/taz signaling validated yap/taz/tead mda-mb-231 nuclear extracts dmba/tpa-treated skin tet1-mediated epigenetic remodeling fshd-related gene 1 fosl2 chip-seq reads ap-1-promoted skin tumorigenesis doxycycline inducible jun-dn oncogenic transcriptional program yap/taz transcriptional response springerlink instant access stem cell biology

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• Modification of enhancer chromatin: what, how, and why?

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         description: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. Piccolo and colleagues report that the YAP/TAZ factors form ternary complexes with TEAD and AP-1 factors to drive a transcriptional program that promotes cell proliferation and tumour growth.
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PostalAddress:
      name:Department of Molecular Medicine, University of Padua School of Medicine, viale Colombo 3 35126 Padua, Italy,
      name:Department of Life Sciences, Center for Genome Research, University of Modena and Reggio Emilia, via G. Campi 287 41100 Modena, Italy,
      name:Department of Molecular Medicine, University of Padua School of Medicine, viale Colombo 3 35126 Padua, Italy,
      name:Department of Molecular Medicine, University of Padua School of Medicine, viale Colombo 3 35126 Padua, Italy,
      name:Department of Molecular Medicine, University of Padua School of Medicine, viale Colombo 3 35126 Padua, Italy,
      name:Genome Biology Unit, Istituto Nazionale di Genetica Molecolare (INGM) ‘Romeo and Enrica Invernizzi’, via Francesco Sforza 35 Milan 20126, Italy,
      name:Department of Surgery, Oncology and Gastroenterology, University of Padua School of Medicine, Via Gattamelata 64 35126 Padua, Italy,
      name:Istituto Oncologico Veneto IOV-IRCCS, Via Gattamelata 64 35126 Padua, Italy,
      name:Department of Life Sciences, Center for Genome Research, University of Modena and Reggio Emilia, via G. Campi 287 41100 Modena, Italy,
      name:Department of Molecular Medicine, University of Padua School of Medicine, viale Colombo 3 35126 Padua, Italy,
      name:Department of Molecular Medicine, University of Padua School of Medicine, viale Colombo 3 35126 Padua, Italy,
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