#40 · Epigenomics

Hi-C-based 3D models resolve ecDNA, nuclear organization and replication timing

The dominant thread across these three publications is the use of Hi-C contact data to build three-dimensional models of genome organization at different scales. ec3D reconstructs the 3D architecture of extrachromosomal DNA by maximizing a Poisson likelihood of observed interactions, reporting spherical configurations and long-range contacts. The integrated 4D Nucleome study of H1 ESC and HFFc6 fibroblasts provides looping catalogues, chromatin domain classes and single-cell 3D models of whole-genome organization. The yeast study extends this framework to DNA replication, using a 3D genome model with replication timing to predict fountain-like fork colocalization, which is then tested against new early S-phase Hi-C data. What is new is the coupling of structural models to replication dynamics, with experimental confirmation of a model prediction in that context, alongside structural modeling of individual extrachromosomal elements.