In addition, while specific patterns of inter-chromosomal interactions might form preferred steady-state structures in differentiated cells it is important to consider how such interactions might be influenced by the formation of chromosomes and their CTs during cell division. Chromosome condensation will inevitably disrupt inter-chromosomal DNA interactions that exist during interphase and so reset the interaction networks to a structural ground-state that will be based on local structure. While DNA foci with,1 Mbp of DNA are widely accepted as fundamental higher-order features of chromosome structure surprisingly little is known about the molecular principles that regulate chromatin function within these structures. Though the formation of foci is unlikely to reflect a LDN-193189 ALK inhibitor single mechanism, it is notable that the foci which form within the euchomatin and heterochromatin compartments are distinct. This is consistent with the local chromatin environment contributing to the structure and stability of individual foci. To test this possibility, we perturbed the local chromatin environment within DNA foci by manipulating the acetylation status of histones using the histone deacetylase inhibitor TSA. After treatment with TSA, under conditions that increased global histone acetylation,5-fold, clear changes in the structure of DNA foci were seen . Notably, foci became more open or dispersed and this correlated with a 4-fold increase in the volume of nuclear domains where DNA from adjacent chromosomes was intermingled. TSA-induced changes in the structure of DNA foci also correlated with a more general disorganization of CTs, which showed widely variable structures and increased size . These experiments show that the chromatin environment contributes to the structure of DNA foci so that when the chromatin environment is perturbed a corresponding deterioration in the structure of DNA foci and CTs is seen. Inside the nucleus, DNA and RNA synthesis are performed within the inter-chromatin compartment, and not within the chromatin-rich DNA foci themselves . Because of this BKM120 moa spatial separation, it is self-evident that chromatin loops must be extruded from the foci towards the active sites during synthesis. This requirement for movement of the chromatin fibre raises the possibility that chromatin loops continually escape from the surface of structural foci in order to probe the inter-chromatin space where favourable synthetic environments might be encountered. During this process, extended chromatin loops from neighboring territories might occupy the same nuclear space and so have a high probability of interacting, for example by binding to a common transcription factory. The analysis presented here suggests that at any time the extended loops represent a very small amount �C,1% or less – of the mammalian genome.