Regulation of chromatin dynamics by a calcium-dependent nucleoskeleton

Growth factors selectively activate calcium signaling pathways in the cell nucleus, which in turn regulate gene transcription and other intranuclear events, but the specific way this is accomplished is not entirely understood. Growth factors increase inositol 1,4,5-trisphosphate (IP3) in the nucleus, which in turn releases calcium from intranuclear IP3 receptors (ITPRs), and the present study shows that this leads to transient assembly of an actin nucleoskeleton that associates with intranuclear non-muscle myosin 2A (MYH9). Mass spectrometry suggests that much of the MYH9 cargo consists of components of the gene transcription machinery, and chromatin immunoprecipitation identified a number of specific genes that associate with the myosin in response to stimulation with growth factors. Together, these findings suggest that growth factors initiate gene transcription by transiently assembling an actin nucleoskeleton that works with MYH9 to bring specific genes to the transcription machinery.