Genome in 3D

In collaboration with the lab of Job Dekker (UMass Medical School at Worchester) we examined architecture of DNA inside the cell. Recently developed method (Hi-C) probes 3D architecture of whole genomes by coupling proximity-based ligation with massively parallel sequencing. This method detects pairwise contacts between distant genomics regions. Our analysis of Hi-C data revealed that at the ~5 Mb scale, chromatin conformation is consistent with the unusual, fractal, non-equilibrium structure: crumpled (fractal) globule, introduced in polymer physics two decades ago. The fractal globule is defined as an unknotted compact polymer structure and is distinct from the classical equilibrium globule state of a polymer that is highly knotted. Using simulations we demonstrated that fractal globule is an attractive model for DNA organization. This knot-free conformation enables maximally dense packing while preserving the ability to easily fold and unfold any genomic locus. Moreover it provides “territorial” DNA organization such that regions close in the genome occupy the same volume in 3D.