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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. doi:10.1371/journal.pcbi.0030210

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

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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, Engineering and Medicine > 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
Official Date: 9 November 2007
Dates:
DateEvent
9 November 2007Published
Volume: Vol.3
Number: No.11
Number of Pages: 8
Page Range: pp. 2135-2142
DOI: 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

Data sourced from Thomson Reuters' Web of Knowledge

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