Transcriptional integration of mitogenic and mechanical signals by Myc and YAP
- Ottavio Croci1,5,
- Serena De Fazio1,5,
- Francesca Biagioni1,5,
- Elisa Donato1,4,5,
- Marieta Caganova1,
- Laura Curti1,
- Mirko Doni2,
- Silvia Sberna1,
- Deborah Aldeghi1,
- Chiara Biancotto1,
- Alessandro Verrecchia2,
- Daniela Olivero3,
- Bruno Amati1,2 and
- Stefano Campaner1
- 1Center for Genomic Science of IIT@SEMM (Istituto Italiano di Tecnologia at European School of Molecular Medicine), Fondazione Istituto Italiano di Tecnologia (IIT), 20139 Milan, Italy;
- 2Department of Experimental Oncology, European Institute of Oncology (IEO), 20139 Milan, Italy;
- 3Laboratorio di Analisi Veterinarie BiEsseA, 20129 Milan, Italy
- Corresponding author: stefano.campaner{at}iit.it
-
↵5 These authors contributed equally to this work.
Abstract
Mammalian cells must integrate environmental cues to determine coherent physiological responses. The transcription factors Myc and YAP–TEAD act downstream from mitogenic signals, with the latter responding also to mechanical cues. Here, we show that these factors coordinately regulate genes required for cell proliferation. Activation of Myc led to extensive association with its genomic targets, most of which were prebound by TEAD. At these loci, recruitment of YAP was Myc-dependent and led to full transcriptional activation. This cooperation was critical for cell cycle entry, organ growth, and tumorigenesis. Thus, Myc and YAP–TEAD integrate mitogenic and mechanical cues at the transcriptional level to provide multifactorial control of cell proliferation.
Keywords
Footnotes
-
Supplemental material is available for this article.
-
Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.301184.117.
-
Freely available online through the Genes & Development Open Access option.
- Received April 28, 2017.
- Accepted October 13, 2017.
This article, published in Genes & Development, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.