TY - JOUR T1 - Colocalization of Coregulated Genes: A Steered Molecular Dynamics Study of Human Chromosome 19 A1 - Di Stefano, Marco A1 - Rosa, Angelo A1 - Belcastro, Vincenzo A1 - di Bernardo, Diego A1 - Micheletti, Cristian Y1 - 2013/03/28 N2 - Author Summary Recent high-throughput experiments have shown that chromosome regions (loci) which accommodate specific sets of coregulated genes can be in close spatial proximity despite their possibly large sequence separation. The findings pose the question of whether gene coregulation and gene colocalization are related in general. Here, we tackle this problem using a knowledge-based coarse-grained model of human chromosome 19. Specifically, we carry out steered molecular dynamics simulations to promote the colocalization of hundreds of gene pairs that are known to be significantly coregulated. We show that most () of such pairs can be simultaneously colocalized. This result is, in turn, shown to depend on at least two distinctive chromosomal features: the remarkably low degree of intra-chain entanglement found in chromosomes inside the nucleus and the large number of cliques present in the gene coregulatory network. The results are therefore largely consistent with the coregulation-colocalization hypothesis. Furthermore, the model chromosome conformations obtained by applying the coregulation constraints are found to display spatial macrodomains that have significant similarities with those inferred from HiC measurements of human chromosome 19. This finding suggests that suitable extensions of the present approach might be used to propose viable ensembles of eukaryotic chromosome conformations in vivo. JF - PLOS Computational Biology JA - PLOS Computational Biology VL - 9 IS - 3 UR - https://doi.org/10.1371/journal.pcbi.1003019 SP - e1003019 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pcbi.1003019 ER -