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Polymer physics of chromosome large-scale 3D organisation

Chiariello, A.M.; Annunziatella, C.; Bianco, S.; Esposito, A.; Nicodemi, M.

Scientific Reports 6: 29775

2016


ISSN/ISBN: 2045-2322
PMID: 27405443
DOI: 10.1038/srep29775
Accession: 072332600

Chromosomes have a complex architecture in the cell nucleus, which serves vital functional purposes, yet its structure and folding mechanisms remain still incompletely understood. Here 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 contact matrix of the Sox9 locus, a region linked to severe human congenital diseases, is derived with high accuracy in mESCs and its molecular determinants identified by the theory; Sox9 self-assembles hierarchically in higher-order domains, involving abundant many-body contacts. Our approach is also applied to the Bmp7 locus. Finally, the model predictions on the effects of mutations on folding are tested against available data on a deletion in the Xist locus. Our results can help progressing new diagnostic tools for diseases linked to chromatin misfolding.

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