Cytoskeletal control of nuclear morphology and chromatin organization.

The nucleus is sculpted toward various morphologies during cellular differentiation and development. Alterations in nuclear shape often result in changes to chromatin organization and genome function. This is thought to be reflective of its role as a cellular mechanotransducer. Recent evidence has highlighted the importance of cytoskeletal organization in defining how nuclear morphology regulates chromatin dynamics. However, the mechanisms underlying cytoskeletal control of chromatin remodeling are not well understood. We demonstrate here the differential influence of perinuclear actin- and microtubule-driven assemblies on nuclear architecture using pharmacological inhibitors and targeted RNA interference knockdown of cytoskeleton components in Drosophila cells. We find evidence that the loss of perinuclear actin assembly results in basolateral enhancement of microtubule organization and this is reflected functionally by enhanced nuclear dynamics. Cytoskeleton reorganization leads to nuclear lamina deformation that influences heterochromatin localization and core histone protein mobility. We also show that modulations in actin-microtubule assembly result in differential gene expression patterns. Taken together, we suggest that perinuclear actin and basolateral microtubule organization exerts mechanical control on nuclear morphology and chromatin dynamics.