Revisiting higher-order and large-scale chromatin organization

The past several years has seen increasing appreciation for plasticity of higher-level chromatin folding. Four distinct '30. nm' chromatin fiber structures have been identified, while new in situ imaging approaches have questioned the universality of 30. nm chromatin fibers as building blocks for chromosome folding in vivo. 3C-based approaches have provided a non-microscopic, genomic approach to investigating chromosome folding while uncovering a plethora of long-distance cis interactions difficult to accommodate in traditional hierarchical chromatin folding models. Recent microscopy based studies have suggested complex topologies co-existing within linear interphase chromosome structures. These results call for a reappraisal of traditional models of higher-level chromatin folding.