Heterogeneous cross-linked polymers to reconstruct chromatin reorganization during cell differentiation
Chromatin of mammalian nucleus folds into discrete contact enriched regions such as Topologically Associating domains (TADs). The folding hierarchy of the TADs and their internal organization is highly dynamic through cellular differentiation, where structural changes within and between TADs are correlated with gene activation and silencing. To account for multiple interacting TADs, we developed a parsimonious randomly cross-linked (RCL) polymer model that maps high frequency encounters present in HiC data within and between TADs into direct local monomer interactions, characterized by the number of cross-links at a given base-pair resolution. We reconstruct three TADs obtained from the mammalian X chromosome for three stages of differentiation. We compute the radius of gyration of TADs and the encounter probability between genomic segments. We found 1) a synchronous compaction and decompaction of TADs throughout differentiation and 2) secondary structures such as meta-TADs in 5C data resulting from weak inter-TAD interactions. Finally, the present method links steady-state to dynamic properties of the chromatin revealed by the distribution of anomalous exponents of single loci trajectories, reconstructed from HiC data.