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Self-assembly and DNA binding of the blocking factor in X chromosome inactivation

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Nicodemi, Mario and Prisco, Antonella. (2007) Self-assembly and DNA binding of the blocking factor in X chromosome inactivation. PLoS Computational Biology, Vol.3 (No.11). pp. 2135-2142. ISSN 1553-734X

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Official URL: http://dx.doi.org/10.1371/journal.pcbi.0030210

Abstract

X chromosome inactivation (XCI) is the phenomenon occurring in female mammals whereby dosage compensation of X-linked genes is obtained by transcriptional silencing of one of their two X chromosomes, randomly chosen during early embryo development. The earliest steps of random X-inactivation, involving counting of the X chromosomes and choice of the active and inactive X, are still not understood. To explain "counting and choice," the longstanding hypothesis is that a molecular complex, a "blocking factor" (BF), exists. The BF is present in a single copy and can randomly bind to just one X per cell which is protected from inactivation, as the second X is inactivated by default. In such a picture, the missing crucial step is to explain how the molecular complex is self-assembled, why only one is formed, and how it binds only one X. We answer these questions within the framework of a schematic Statistical Physics model, investigated by Monte Carlo computer simulations. We show that a single complex is assembled as a result of a thermodynamic process relying on a phase transition occurring in the system which spontaneously breaks the symmetry between the X’s. We discuss, then, the BF interaction with X chromosomes. The thermodynamics of the mechanism that directs the two chromosomes to opposite fates could be, thus, clarified. The insights on the selfassembling and X binding properties of the BF are used to derive a quantitative scenario of biological implications describing current experimental evidences on "counting and choice."

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, Gene silencing -- Computer simulation
Journal or Publication Title:	PLoS Computational Biology
Publisher:	Public Library of Science
ISSN:	1553-734X
Date:	9 November 2007
Volume:	Vol.3
Number:	No.11
Number of Pages:	8
Page Range:	pp. 2135-2142
Identification Number:	10.1371/journal.pcbi.0030210
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open 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), Network MRTN-CT-2003–504712
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URI:	http://wrap.warwick.ac.uk/id/eprint/30920