He same TAD or R 115777 site insulated domain. Even though TAD organization is often conserved among cell types, looping interactions can be cell type specific, but do rarely seem to cross TAD boundaries. The presence of a looping interaction can alter gene expression in a cell type specific manner by bringing promoters in close proximity to promoters. Looping interactions have been suggested to function as a fine-tuning mechanism of regulation. It has been shown for several diseases, like cancer and polydactyly, how alteration in looping interactions is associated with the disease phenotype. To summarize, interphase PR 619 chromatin architecture is established by clustering of sets of TADs into cell type specific A and PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19857213 B compartments. The cell type specific regulation of a certain locus within a TAD is then enabled by forming loops of for example regulating loci with an effector locus. This partly cell type specific conformation of interphase chromosomes changes dramatically during mitosis. Observations using microscopy techniques already proved the dramatic changes many decades ago. The distribution of the DNA in the nucleus changes from amorphous territories to elongated rode shaped structures, with the characteristic banding pattern upon staining. It was shown that these mitotic bands along the chromosomes are the same between different cell types. Both the dramatic change in shape and the cell type indifferent band patterns already suggested loss of the higher organization in compartments and TADs known for interphase chromosomes, as the rod shape and the individualization of the chromosomes do not allow for interaction within and between compartments. Using 5C and Hi-Ctechniques Naumova et al. observed these dramatic changes in a genome wide manner, represented in figure 2c. Clearly, cells are capable of reestablishing the same chromosomal organization in early G1 phase as was present before mitosis. A recent study of Hsuing et al measured enhancer promoter interactions in interphase and mitosis using Capture-C, a technique to capture interactions anchored at hundreds of loci at the same time. For the promoter enhancer pairs measured in this study, it was found that they are specific to interphase, and show to have largely reduced interaction frequencies in mitotic cells. This suggests that chromosomal organization in loops between functional elements is also impaired in mitosis, and that these interactions must be re-established in the next G1 phase. Folding of the mitotic chromosome Although the folding characteristics of interphase chromatin appear almost completely lost during mitosis, this does not mean mitotic chromatin has no higher order organization. The mitotic chromosome of vertebrates condenses 23 times in volume compared to interphase Author Manuscript Author Manuscript Author Manuscript Author Manuscript Crit Rev Biochem Mol Biol. Author manuscript; available in PMC 2017 June 02. Oomen and Dekker Page 6 . The prevailing model for mitotic chromosome architecture that is supported by pioneering microscopy studies by Laemmli and co-workers, more recent 5C and Hi-C analyses and polymer modeling is that chromosomes fold as longitudinally compressed arrays or stochastically positioned consecutive chromatin loops. Furthermore, during the condensation process, sister chromatids are separated and individualized during pro- and prometaphase to accommodate proper division over the two new daughter cells. The main machineries that drive mitotic chro.He same TAD or insulated domain. Even though TAD organization is often conserved among cell types, looping interactions can be cell type specific, but do rarely seem to cross TAD boundaries. The presence of a looping interaction can alter gene expression in a cell type specific manner by bringing promoters in close proximity to promoters. Looping interactions have been suggested to function as a fine-tuning mechanism of regulation. It has been shown for several diseases, like cancer and polydactyly, how alteration in looping interactions is associated with the disease phenotype. To summarize, interphase chromatin architecture is established by clustering of sets of TADs into cell type specific A and PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19857213 B compartments. The cell type specific regulation of a certain locus within a TAD is then enabled by forming loops of for example regulating loci with an effector locus. This partly cell type specific conformation of interphase chromosomes changes dramatically during mitosis. Observations using microscopy techniques already proved the dramatic changes many decades ago. The distribution of the DNA in the nucleus changes from amorphous territories to elongated rode shaped structures, with the characteristic banding pattern upon staining. It was shown that these mitotic bands along the chromosomes are the same between different cell types. Both the dramatic change in shape and the cell type indifferent band patterns already suggested loss of the higher organization in compartments and TADs known for interphase chromosomes, as the rod shape and the individualization of the chromosomes do not allow for interaction within and between compartments. Using 5C and Hi-Ctechniques Naumova et al. observed these dramatic changes in a genome wide manner, represented in figure 2c. Clearly, cells are capable of reestablishing the same chromosomal organization in early G1 phase as was present before mitosis. A recent study of Hsuing et al measured enhancer promoter interactions in interphase and mitosis using Capture-C, a technique to capture interactions anchored at hundreds of loci at the same time. For the promoter enhancer pairs measured in this study, it was found that they are specific to interphase, and show to have largely reduced interaction frequencies in mitotic cells. This suggests that chromosomal organization in loops between functional elements is also impaired in mitosis, and that these interactions must be re-established in the next G1 phase. Folding of the mitotic chromosome Although the folding characteristics of interphase chromatin appear almost completely lost during mitosis, this does not mean mitotic chromatin has no higher order organization. The mitotic chromosome of vertebrates condenses 23 times in volume compared to interphase Author Manuscript Author Manuscript Author Manuscript Author Manuscript Crit Rev Biochem Mol Biol. Author manuscript; available in PMC 2017 June 02. Oomen and Dekker Page 6 . The prevailing model for mitotic chromosome architecture that is supported by pioneering microscopy studies by Laemmli and co-workers, more recent 5C and Hi-C analyses and polymer modeling is that chromosomes fold as longitudinally compressed arrays or stochastically positioned consecutive chromatin loops. Furthermore, during the condensation process, sister chromatids are separated and individualized during pro- and prometaphase to accommodate proper division over the two new daughter cells. The main machineries that drive mitotic chro.