Geometric Regulation of Chromatin Remodeling is Dependent on Acto-Myosin Contractility

Abstract

Cells and tissues respond to geometric constraints by altering their gene expression programs. Modulation of gene expression requires post-translational modifications, such as histone acetylation, to alter chromatin compaction states and hence accessibility to gene regulatory sites for transcriptional machinery. But the mechanisms underlying geometrical constraints impinging on chromatin remodeling is largely unknown. In this work we show that cellular geometric constraints impinge on both the spatial organization of actin cytoskeleton and nuclear morphology (shape and size). These changes are found to be dependent on acto-myosin contractility as revealed by the phosphorylation of myosin light chain kinase (MLCK). Further geometric constraints regulate the nuclear to cytoplasmic ratio of HDAC3, a histone-deacetylase enzyme. Taken together, our work suggests that cellular geometric cues regulate chromatin remodeling processes via modulating acto-myosin contractility and nuclear-cytoplasmic shuttling of histone deceatylase enzymes.