In mammals, clear identification of active and null domains is evident, while Polycomb and Hp1 domains, if exists, are likely to be smaller than 1MB in scale, making their detection using current maps difficult. The correlations between 3C domain structure and epigenomic datasets pave the way to better integrative models in epigenomics. The notoriously complex and indirect correlations between the many measurable aspects of epigenomic structure can
now be overlaid on top of 3C contact maps, putting ABT-263 supplier epigenetic and regulatory marks onto a model reflecting short-range and long-range contacts. The a priori independence of 3C maps from other epigenomic profiling techniques, and its two-dimensional natural matrix structure, suggest these EGFR inhibitors list maps can become
a standard basis for epigenomic exploration, even before the precise physical basis of their domain structure is fully resolved. 3C-Domains: physical structure and insulation. Regardless of their immediate utility, the association between 3C-domains and chromosomal structure remains unclear ( Figure 2). In principle, the 3C-contact frequency of two chromosomal elements is linked with the distribution of their intra-nucleus physical distances, but the nature of this linkage can involve non-linear effects and proximity thresholds. For instance, the linkage signal may decrease with increasing distance following a certain quantitative regime up to a certain threshold but then be observed to follow a different regime for longer range contacts. Moreover, linkage may be affected by other factors that
are unrelated to distance at all, such as the average contact time between the interacting partners. A 3C domain is defined by an enrichment of 3C contacts inside a chromosomal (linear) domain, suggesting that elements within the domain are folded into compact structures. However, 3C contacts do not represent an absolute measure of distance, but reflect a competitive process of ligating exposed restriction fragments. Given this viewpoint, a 3C domain Dichloromethane dehalogenase may be formed without any particular compaction, provided that elements within a certain chromosomal domains are insulated from their genomic surroundings and are thereby more likely to form contact between themselves. Indeed, high resolution analysis in Drosophila have shown that almost all 3C-domains are bordered by binding sites of insulating factors (including, in Drosophila, CP190, its cooperating sequence specific factors, and Chromator). Similar observations are emerging from lower resolution mammalian maps [ 6••].
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