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 di erent 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 identi ed 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 e ects 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.

Polymer physics of chromosome large-scale 3D organisation / Chiariello, A. M.; Bianco, S.; Annunziatella, C.; Esposito, A.; Nicodemi, M.. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 6:1(2016), p. 29775. [DOI: 10.1038/srep29775]

Polymer physics of chromosome large-scale 3D organisation

A. M. Chiariello
Co-primo
;
S. Bianco
Co-primo
;
A. Esposito;M. Nicodemi
2016

Abstract

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 di erent 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 identi ed 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 e ects 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.
2016
Polymer physics of chromosome large-scale 3D organisation / Chiariello, A. M.; Bianco, S.; Annunziatella, C.; Esposito, A.; Nicodemi, M.. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 6:1(2016), p. 29775. [DOI: 10.1038/srep29775]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/659459
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