Andrea Maria Chiarello — Università degli Studi di Napoli "Faderico II" #
Structural organization of chromosomes and computational methods to reconstruct its 3D architecture #
Chromosomes have a complex architecture in the cell nucleus, which serves vital functional purposes, yet its structure and folding mechanisms remain still incompletely understood. We show that genome-wide chromatin architecture data, as mapped by Hi-C methods across mammalian cell types and chromosomes, are well described by classical scaling concepts of polymer physics, from the sub-Mb to chromosomal scales. Chromatin is a complex mixture of different regions, folded in the conformational classes predicted by polymer thermodynamics. The 3D structure of various loci, important to the genome functionality, are derived with high accuracy; for instance, the Sox9 locus self-assembles hierarchically in higher-order domains, involving abundant many-body contacts. Finally, the model predictions on the effects of mutations on folding are tested against experimental data.

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