Current theoretical models fail to predict the topological complexity of the human genome

Understanding the folding of the human genome is a key challenge of modern structural biology. The emergence of chromatin conformation capture assays (e.g., Hi-C) has revolutionized chromosome biology and provided new insights into the three dimensional structure of the genome. The experimental data...

Full description

Saved in:

Bibliographic Details
Published in:	Frontiers in molecular biosciences Vol. 2; p. 48
Main Authors:	Arsuaga, Javier, Jayasinghe, Reyka G, Scharein, Robert G, Segal, Mark R, Stolz, Robert H, Vazquez, Mariel
Format:	Journal Article
Language:	English
Published:	Switzerland Frontiers Media S.A 21-08-2015
Subjects:	BFACF chromosome organization DNA knotting equilibrium globule Hic Lattice models Molecular Biosciences BFACF lattice models chromosome organization Hi-C equilibrium globule DNA knotting
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Understanding the folding of the human genome is a key challenge of modern structural biology. The emergence of chromatin conformation capture assays (e.g., Hi-C) has revolutionized chromosome biology and provided new insights into the three dimensional structure of the genome. The experimental data are highly complex and need to be analyzed with quantitative tools. It has been argued that the data obtained from Hi-C assays are consistent with a fractal organization of the genome. A key characteristic of the fractal globule is the lack of topological complexity (knotting or inter-linking). However, the absence of topological complexity contradicts results from polymer physics showing that the entanglement of long linear polymers in a confined volume increases rapidly with the length and with decreasing volume. In vivo and in vitro assays support this claim in some biological systems. We simulate knotted lattice polygons confined inside a sphere and demonstrate that their contact frequencies agree with the human Hi-C data. We conclude that the topological complexity of the human genome cannot be inferred from current Hi-C data.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by: Guowei Wei, Michigan State University, USA Reviewed by: Guillaume Witz, Harvard University, USA; Graziano Vernizzi, Siena College, USA This article was submitted to Mathematics of Biomolecules, a section of the journal Frontiers in Molecular Biosciences
ISSN:	2296-889X 2296-889X
DOI:	10.3389/fmolb.2015.00048