Tuesday 23
Restraint-based modeling of the 3d folding

› 16:45 - 17:30 (45min)
Colocalization of coregulated genes: A steered molecular dynamics study of Human Chromosome 19
Marco Di Stefano  1@  
1 : Scuola Internazionale Superiore di Studi Avanzati / International School for Advanced Studies  (SISSA / ISAS)  -  Website
via Bonomea, 265 - 34136 Trieste - Italy -  Italy

The observation that the concerted activity of certain groups of genes significantly correlates with their proximity in the nucleus [1] poses the general question of whether it is at all feasible to bring close together the numerous coregulated gene pairs on a chromosome. We tested this hypothesis by using steered molecular dynamics simulations of a coarse-grained (30nm) model for the gene-rich human chromosome 19. We enforced the colocalization of ~1,500 pairs of genes, whose expression patterns over ~20,000 microarray experiments are significantly correlated (coregulation).

Remarkably, we showed that the vast majority (~82%) of the target gene pairings can be accomplished. This was found to depend on: (1) the low degree of entanglement in chromatin fibers, and (2) the large number of cliques (genes coregulated all together as groups) in the gene coregulatory network. Finally, the chromosome organization from the steering procedure was shown to be arranged in spatial macro-domains, similar to those inferred from Hi-C experimental data.

These findings indicate that gene coregulation and colocalization are largely compatible, and that our computational strategy can be further applied to draft the spatial organization of chromosomes in other eukaryotes [2].



.[1] G. Cavalli, Curr. Opin. Genet. Dev. 17, 443 (2007)

.[2] M. Di Stefano, A. Rosa, V. Belcastro, D. di Bernardo, C. Micheletti, PLoS Comput. Biol. 9, e1003019 (2013)

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