title: Polymer physics of chromosome large-scale 3D organisation.
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.
authors.affiliation: Dipartimento di Fisica, Università di Napoli Federico II, and INFN Napoli, CNR-SPIN, Complesso Universitario di Monte Sant'Angelo, 80126 Naples, Italy.
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Chiariello
authors.affiliation: Dipartimento di Fisica, Università di Napoli Federico II, and INFN Napoli, CNR-SPIN, Complesso Universitario di Monte Sant'Angelo, 80126 Naples, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Annunziatella
authors.affiliation: Dipartimento di Fisica, Università di Napoli Federico II, and INFN Napoli, CNR-SPIN, Complesso Universitario di Monte Sant'Angelo, 80126 Naples, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Bianco
authors.affiliation: Dipartimento di Fisica, Università di Napoli Federico II, and INFN Napoli, CNR-SPIN, Complesso Universitario di Monte Sant'Angelo, 80126 Naples, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Esposito
authors.affiliation: Dipartimento di Fisica, Università di Napoli Federico II, and INFN Napoli, CNR-SPIN, Complesso Universitario di Monte Sant'Angelo, 80126 Naples, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Nicodemi
mesh_terms: D000818:Animals; D002843:Chromatin / Q000737:chemistry* / Q000378:metabolism; D002877:Chromosomes, Human / Q000737:chemistry* / Q000378:metabolism; D056426:Genetic Loci; D006801:Humans; D051379:Mice; D055758:SOX9 Transcription Factor / Q000737:chemistry / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D002843:Chromatin; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; C527933:Sox9 protein, mouse