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

By Mario Nicodemi and Antonella Prisco


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

Topics: QH426
Publisher: Public Library of Science
Year: 2007
OAI identifier: oai:wrap.warwick.ac.uk:30920

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  4. (1997). Applications of Monte Carlo methods to statistical physics. doi
  5. (1997). Ashworth A
  6. (2002). Autosomal dominant mutations affecting X inactivation choice in the mouse.
  7. (2005). Chromatin remodeling in dosage compensation. doi
  8. (1999). Conditional deletion of Xist disrupts histone macroH2A localization but not maintenance of X inactivation.
  9. (2003). Coordination of the random asynchronous replication of autosomal loci. doi
  10. (1961). Gene action in the X-chromosome of the mouse (Mus musculus L.). doi
  11. (2002). Homozygous Tsix mutant mice reveal a sex-ratio distortion and revert to random X-inactivation. doi
  12. (2007). Identification of a Ctcf cofactor, Yy1, for the X chromosome binary switch. doi
  13. (1971). Introduction to phase transitions and critical phenomena. Gloucestershire (United Kingdom):
  14. (1983). Mammalian X-chromosome inactivation. doi
  15. (1993). Mapping the murine Xce locus with (CA)n repeats. doi
  16. (2003). Molecular biology of the gene.
  17. (1983). Non-random X-chromosome inactivation in mouse Xautosome translocation embryos location of the inactivation centre.
  18. (2007). Prisco A doi
  19. (2001). Regulation of imprinted Xchromosome inactivation in mice by Tsix.
  20. (2005). Regulation of X-chromosome counting by Tsix and Xite sequences. doi
  21. (1998). Role of the region 39 to Xist exon 6 in the counting process of X chromosome inactivation. doi
  22. (1998). Role of the Xist gene in X chromosome choosing. doi
  23. (2005). Silencing of the mammalian X chromosome. doi
  24. (1999). Targeted mutagenesis of Tsix leads to nonrandom X inactivation. doi
  25. (2007). The DXPas34 repeat regulates random and imprinted X inactivation. doi
  26. (2004). The region 39 to Xist mediates X chromosome counting and H3 Lys-4 dimethylation within the Xist gene. doi
  27. (2006). Transient colocalization of X-inactivation centres accompanies the initiation of X inactivation. doi
  28. (2006). Transient homologous chromosome pairing marks the onset of X inactivation. doi
  29. (2001). Tsix-mediated repression of Xist accumulation is not sufficient for normal random X inactivation. doi
  30. (2005). X chromosome choice occurs independently of asynchronous replication timing. doi
  31. (1972). X-chromosome inactivation and developmental patterns in mammals. doi
  32. (2002). X-chromosome inactivation and human genetic disease. doi
  33. (2001). X-chromosome inactivation: counting, choice and initiation.
  34. (1999). Xist Yeast artificial chromosome transgenes functions as Xinactivation centers only in multicopy arrays and not as single copies.

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