Symmetry-breaking model for X-chromosome inactivation (Articolo in rivista)

  • Symmetry-breaking model for X-chromosome inactivation (Articolo in rivista) (literal)
  • 2007-01-01T00:00:00+01:00 (literal)
  • 10.1103/PhysRevLett.98.108104 (literal)
Alternative label
  • Nicodemi M.; Prisco A. (2007)
    Symmetry-breaking model for X-chromosome inactivation
    in Physical review letters (Print)
  • Nicodemi M.; Prisco A. (literal)
Pagina inizio
  • 104 (literal)
Pagina fine
  • 108 (literal)
  • All'articolo è stato dedicato un News and Views su Nature Physics \"The ilence of the chromosomes\" Alison Wright vol 3 April 2007, p 221 (literal)
  • 98 (literal)
  • 10 (literal)
  • Pubblicazione (literal)
  • Scopu (literal)
  • ISI Web of Science (WOS) (literal)
  • PubMe (literal)
  • Dipartimento di Scienze Fisiche, Universita` di Napoli ''Federico II,'' INFN, Via Cintia, 80126 Napoli, Italy CNR Institute of Genetics and Biophysics \"Buzzati Traverso,\" Via Pietro Castellino 111, 80131 Napoli, Italy (literal)
  • Symmetry-breaking model for X-chromosome inactivation (literal)
  • In mammals, dosage compensation of X linked genes in female cells is achieved by inactivation of one of their two X chromosomes which is randomly chosen. The earliest steps in X-chromosome inactivation (XCI), namely, the mechanism whereby cells count their X chromosomes and choose between two equivalent X chromosomes, remain mysterious. Starting from the recent discovery of X chromosome colocalization at the onset of X-chromosome inactivation, we propose a statistical mechanics model of XCI, which is investigated by computer simulations and checked against experimental data. Our model describes how a \"blocking factor\" complex is self-assembled and why only one is formed out of many diffusible molecules, resulting in a spontaneous symmetry breaking in the binding to two identical chromosomes. These results are used to derive a scenario of biological implications. (literal)
  • 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 self-assembling 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.” (literal)
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