Dynamic regulation of chromatin structure is thought to be a prerequisite for nuclear functions that require accessibility to DNA such as replication, transcription and DNA repair. The phosphoinositide (PI) pathway is a second messenger signalling system regulated in response to a variety of extracellular (growth factors, differentiation signals) and intracellular (cell cycle progression, DNA damage) stimuli. The presence of a PI pathway in the nucleus together with the recent findings that specific nuclear proteins can interact with and are regulated by phosphoinositides suggest that changes in the nuclear phosphoinositide profile may have a direct role in modulating chromatin structure.