Differentiation and large scale spatial organization of the genome.

The spatial organization of the genome plays an important role in the regulation of nuclear functions and undergoes large scale changes during differentiation. These changes in the nuclear distribution of chromatin are, in a complex way, related to transcriptional status and epigenetic modifications. Recent studies emphasize the roles that gene promoters and alterations in replication timing play in the spatial reorganization of chromatin during cell differentiation. Changes in the association of chromatin regions with the nuclear lamina also emerge as a significant factor of transcriptional regulation. New results suggest that the spatial organization of chromatin in embryonic stem cells may be important for maintenance of the pluripotent state, whereas the nuclear architecture of differentiated cells facilitates formation of transcriptionally active zones with shared transcription and splicing machinery.