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Activation of X Chromosome Inactivation
- Publication date
- 6 December 2016
- Publisher
- In mammals, males are the heterogametic sex having an X chromosome and a Y chromosome whereas females have two X chromosomes. Despite originating from an ancient homologous autosomal pair, the X and Y chromosome now differ greatly in size and gene content after ~180 MY of evolution. The X chromosome retained over 1000 genes, whereas the Y chromosome degenerated over time and only contains about a hundred genes mainly involved in male spermatogenesis. Females have two X chromosomes and thus double the amount of X-encoded genes as compared to males which creates an imbalance of X-encoded genes between males and females. Mammals achieve dosage compensation of this imbalance of X-encoded genes by inactivating one of the two X chromosomes in female cells by a process called X chromosome inactivation (XCI). XCI is a stochastic process in which each X chromosome has an equal probability to be inactivated. Even though XCI is stochastic, it is a tightly regulated process to obtain one active X chromosome per diploid genome. Regulation of XCI is achieved by the X inactivation center (Xic), located on the X chromosome, which harbors all the necessary elements for XCI to occur. These elements are regulated by XCI activators and inhibitors. The aim of this thesis is to gain more insight into the molecular me