In addition to soluble factors, mechanical constraints and extracellular matrix stiffness are important regulators of cell fate that are mediated by cytoskeletal modifications. The EMT (epithelial–mesenchymal transition) that occurs during normal development and malignant progression is a typical example of the phenotypic switch associated with profound actin remodelling and changes in gene expression. For instance, actin dynamics control motile cell functions in EMT, in part, through regulating the subcellular localization of the myocardin-related transcription factor MKL1 (megakaryoblastic leukaemia translocation 1), a co-activator of SRF (serum-responsive factor). In the present paper, we show that MKL1 participates also to the control of the cellular switch between growth and quiescence. Experimental disconnection between MKL1 and G-actin (globular actin), by using an MKL1 mutant or enhancing the F (filamentous)-/G-actin ratio, generates a widely open chromatin state and a global increase in biosynthetic activity, classically associated with cell growth. Conversely, G-actin accumulation favours nuclear condensation and cell quiescence. These large-scale chromatin changes rely upon extensive histone modifications, exemplified by that of H3K9 (H3 Lys9) shifting from trimethylation, a heterochromatin mark, to acetylation, a mark of euchromatin. The present study provides the first evidence for a global reversible hetero/euchromatinization phenomenon triggered by the actin/MKL1 signalling pathway.
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Research Article|
June 26 2014
The actin/MKL1 signalling pathway influences cell growth and gene expression through large-scale chromatin reorganization and histone post-translational modifications
Gilles Flouriot;
Gilles Flouriot
1
*University of Rennes 1, Institut de Recherche en Santé, Environnement et Travail, IRSET, INSERM U1085, Team TREC, Biosit, Rennes, France
1To whom correspondence should be addressed (email gilles.flouriot@univ-rennes1.fr).
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Guillaume Huet;
Guillaume Huet
*University of Rennes 1, Institut de Recherche en Santé, Environnement et Travail, IRSET, INSERM U1085, Team TREC, Biosit, Rennes, France
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Florence Demay;
Florence Demay
*University of Rennes 1, Institut de Recherche en Santé, Environnement et Travail, IRSET, INSERM U1085, Team TREC, Biosit, Rennes, France
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Farzad Pakdel;
Farzad Pakdel
*University of Rennes 1, Institut de Recherche en Santé, Environnement et Travail, IRSET, INSERM U1085, Team TREC, Biosit, Rennes, France
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Noureddine Boujrad;
Noureddine Boujrad
*University of Rennes 1, Institut de Recherche en Santé, Environnement et Travail, IRSET, INSERM U1085, Team TREC, Biosit, Rennes, France
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Denis Michel
Denis Michel
*University of Rennes 1, Institut de Recherche en Santé, Environnement et Travail, IRSET, INSERM U1085, Team TREC, Biosit, Rennes, France
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Publisher: Portland Press Ltd
Received:
September 19 2013
Revision Received:
April 03 2014
Accepted:
April 24 2014
Accepted Manuscript online:
April 24 2014
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2014 Biochemical Society
2014
Biochem J (2014) 461 (2): 257–268.
Article history
Received:
September 19 2013
Revision Received:
April 03 2014
Accepted:
April 24 2014
Accepted Manuscript online:
April 24 2014
Citation
Gilles Flouriot, Guillaume Huet, Florence Demay, Farzad Pakdel, Noureddine Boujrad, Denis Michel; The actin/MKL1 signalling pathway influences cell growth and gene expression through large-scale chromatin reorganization and histone post-translational modifications. Biochem J 15 July 2014; 461 (2): 257–268. doi: https://doi.org/10.1042/BJ20131240
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