Polymer physics of chromosome large-scale 3D organisation View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-07-13

AUTHORS

Andrea M. Chiariello, Carlo Annunziatella, Simona Bianco, Andrea Esposito, Mario Nicodemi

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 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. More... »

PAGES

29775

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/srep29775

DOI

http://dx.doi.org/10.1038/srep29775

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1028981829

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27405443


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