Ontology type: schema:ScholarlyArticle Open Access: True
2016-07-13
AUTHORSAndrea M. Chiariello, Carlo Annunziatella, Simona Bianco, Andrea Esposito, Mario Nicodemi
ABSTRACTChromosomes 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... »
PAGES29775
http://scigraph.springernature.com/pub.10.1038/srep29775
DOIhttp://dx.doi.org/10.1038/srep29775
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PUBMEDhttps://www.ncbi.nlm.nih.gov/pubmed/27405443
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