Nicodemi, Mario and Prisco, Antonella (2009) Thermodynamic pathways to genome spatial organization in the cell nucleus. Biophysical Journal, Vol.96 (No.6). pp. 2168-2177. doi:10.1016/j.bpj.2008.12.3919

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Abstract

The architecture of the eukaryotic genome is characterized by a high degree of spatial organization. Chromosomes occupy preferred territories correlated to their state of activity and, yet, displace their genes to interact with remote sites in complex patterns requiring the orchestration of a huge number of DNA loci and molecular regulators. Far from random, this organization serves crucial functional purposes, but its governing principles remain elusive. By computer simulations of a Statistical Mechanics model, we show how architectural patterns spontaneously arise from the physical interaction between soluble binding molecules and chromosomes via collective thermodynamics mechanisms. Chromosomes colocalize, loops and territories form and find their relative positions as stable hermodynamic states. These are selected by “thermodynamic switches” which are regulated by concentrations/affinity of soluble mediators and by number/location of their attachment sites along chromosomes. Our “thermodynamic switch model” of nuclear architecture, thus, explains on quantitative grounds how well known cell strategies of upregulation of DNA binding proteins or modification of chromatin structure can dynamically shape the organization of the nucleus.

Item Type:	Journal Article
Subjects:	Q Science > QH Natural history > QH426 Genetics
Divisions:	Faculty of Science > Physics
Library of Congress Subject Headings (LCSH):	Eukaryotic cells -- Genetics, Genomics, Binding sites (Biochemistry) -- Thermodynamics, Chromosomes -- Analysis
Journal or Publication Title:	Biophysical Journal
Publisher:	Biophysical Society
ISSN:	0006-3495
Official Date:	2009
Dates:	Date Event 2009 Published
Volume:	Vol.96
Number:	No.6
Page Range:	pp. 2168-2177
DOI:	10.1016/j.bpj.2008.12.3919
Status:	Peer Reviewed
Access rights to Published version:	Restricted or Subscription Access
Funder:	Italy. Ministero dell'istruzione, dell'università e della ricerca (MIUR), Fondo per gli Investimenti della Ricerca di Base (FIRB)
Grant number:	RBNE01S29H (MIUR-FIRB)

Data sourced from Thomson Reuters' Web of Knowledge

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