EMAIL THIS PAGE TO A FRIEND

The Biochemical journal

The actin/MKL1 signalling pathway influences cell growth and gene expression through large-scale chromatin reorganization and histone post-translational modifications.


PMID 24762104

Abstract

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.

Related Materials

Product #

Image

Description

Molecular Formula

Add to Cart

SAB2502098
Anti-PCNA antibody produced in goat, affinity isolated antibody, buffered aqueous solution
SAB2502099
Anti-PCNA antibody produced in goat, affinity isolated antibody, buffered aqueous solution
AV03018
Anti-PCNA antibody produced in rabbit, IgG fraction of antiserum
HPA030521
Anti-PCNA antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution, ab1
HPA030522
Anti-PCNA antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution, ab2
HPA030523
Anti-PCNA antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution, ab3
SAB2701819
Anti-PCNA antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
SAB4502103
Anti-PCNA antibody produced in rabbit, affinity isolated antibody
EHU003471 MISSION® esiRNA, esiRNA targeting human SRF (esiRNA1)
WH0005111M2
Monoclonal Anti-PCNA antibody produced in mouse, clone 1G7, purified immunoglobulin, buffered aqueous solution
SAB1404178
Monoclonal Anti-PCNA antibody produced in mouse, clone S1, purified immunoglobulin, buffered aqueous solution
SAB4100556
Monoclonal Anti-PCNA antibody produced in mouse, clone PCNA -A509, culture supernatant
PLA0079
Rabbit anti-PCNA Antibody, Affinity Purified, Powered by Bethyl Laboratories, Inc.
PLA0080
Rabbit anti-PCNA Antibody, Affinity Purified, Powered by Bethyl Laboratories, Inc.