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Mechanics and dynamics of X-chromosome pairing at X inactivation

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Scialdone, Antonio and Nicodemi, Mario. (2008) Mechanics and dynamics of X-chromosome pairing at X inactivation. PL o S Computational Biology, Vol.4 (No.12). ISSN 1553-734X

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Official URL: http://dx.doi.org/10.1371/journal.pcbi.1000244

Abstract

At the onset of X-chromosome inactivation, the vital process whereby female mammalian cells equalize X products with respect to males, the X chromosomes are colocalized along their Xic (X-inactivation center) regions. The mechanism inducing recognition and pairing of the X’s remains, though, elusive. Starting from recent discoveries on the molecular factors and on the DNA sequences (the so-called "pairing sites") involved, we dissect the mechanical basis of Xic colocalization by using a statistical physics model. We show that soluble DNA-specific binding molecules, such as those experimentally identified, can be indeed sufficient to induce the spontaneous colocalization of the homologous chromosomes but only when their concentration, or chemical affinity, rises above a threshold value as a consequence of a thermodynamic phase transition. We derive the likelihood of pairing and its probability distribution. Chromosome dynamics has two stages: an initial independent Brownian diffusion followed, after a characteristic time scale, by recognition and pairing. Finally, we investigate the effects of DNA deletion/insertions in the region of pairing sites and compare model predictions to available experimental data.

Item Type:	Journal Article
Subjects:	Q Science > QH Natural history > QH426 Genetics
Divisions:	Faculty of Science > Physics
Library of Congress Subject Headings (LCSH):	X chromosome
Journal or Publication Title:	PL o S Computational Biology
Publisher:	Public Library of Science
ISSN:	1553-734X
Date:	26 December 2008
Volume:	Vol.4
Number:	No.12
Number of Pages:	7
Identification Number:	10.1371/journal.pcbi.1000244
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access
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URI:	http://wrap.warwick.ac.uk/id/eprint/28364