L’inactivation du chromosome X

old_uid7912
titleL’inactivation du chromosome X
start_date2010/01/08
schedule14h-15h30
onlineno
summaryIn female mammals, one of the two X chromosomes is converted from the active euchromatic state into inactive heterochromatin during early embryonic development. This process, known as X-chromosome inactivation, results in the transcriptional silencing of over a thousand genes and ensures dosage compensation between the sexes. X inactivation is a dramatic example of mammalian epigenetics, involving differential regulation of two homologous chromosomes within the same nucleus, in a mitotically heritable but developmentally reversible manner. We are interested in the mechanisms and kinetics of this process in early mouse embryos and differentiating embryonic stem (ES) cells. In particular, we have found that X inactivation is a highly dynamic process during early development and are defining the epigenetic marks that underlie its initiati! on and its maintenance. Given the monoallelic character of X inactivation, we are also investigating the role of sub-nuclear compartmentalization in this process, both at the level of the master control locus of X inactivation, the Xic, and the non-coding Xist transcript it produces, that is responsible for inducing transcriptional silencing in cis. Our recent studies have shown that the two Xics homologously pair transiently during the initiation of X inactivation and that this could provide a mechanism for the cell to “sense” the number of X chromosomes that are present and to trigger X inactivation by monoallelic up-regulation of Xist. We have also demonstrated that Xist RNA may have a role in spatially segregating and reorganizing the X chromosome in the nucleus during X inactivation. Finally we are also interested in the evolution of X inactivation and have recently found that there is a substantial diversity in the regulation of this process during development between mammals.
responsiblesNicoglou, Viciana