Consequently, inter-chromosomal contacts are about 70 times less frequent than intra-chromosomal contacts and may be present only in a fraction of cells where both interacting regions are accessible [41] (Figure 1). The fractal globule model has provided exciting initial insights into genome-wide short-range and long-range gene interactions involved in transcriptional regulation and chromosomal translocations in cancer. However, current 3C methodology surveys chromatin topology

within dynamic populations of cells. At the single cell level, chromatin interactions are likely to be dynamic, some being stochastic, and their frequency may depend on the cell cycle and additional factors. Therefore, an examination of chromatin topology of single cells is needed to assess cell-to-cell differences as well as changes during the cell cycle DAPT research buy and stages of differentiation in order to fully understand the relationship of gene interactions to cellular function. From the higher order fractal globule structure, chromatin is further selleck compound organized into chromosome

territories, where each chromosome, rather than being intertwined, occupies its own distinct region of the nucleus (reviewed in [42 and 43]). In order to study the contacts and interdigitation of chromosome territories, Bickmore and colleagues used fluorescently-labeled pooled sequence-capture probes to show that the exons of mouse chromosome 2 predominantly localize at the surface of the chromosome territory [44]. This is consistent with genes looping out of their chromosome territory and allows for interactions with regions of other chromosomes. Pulse-labeling experiments have revealed that only 1% of chromatin from different chromosomes co-localize in

interphase cells [45]. Thus it is likely that these inter-chromosomal interactions occur transiently and/or that these are rare events, as has also been proposed by genome-wide mapping of Farnesyltransferase chromosome interactions [41] (Figure 1). The importance of inter-chromosomal interactions for gene regulation still remains to be elucidated, but it has been proposed that some co-regulated genes can colocalize in interchromatin granules or transcription factories [46, 47 and 48]. However, it remains to be demonstrated if looping out from a chromosome territory is an active process preceding transcription, or if it is a consequence of gene activation (Figure 2). Treatment with the histone deacetylase inhibitor TSA results in increased chromatin mobility [49] and an increase in inter-chromosomal co-localization [45], suggesting that gene activation may not be a consequence of gene movement and co-localization, and that the two processes might indeed be independent from each other (Figure 2c).