| In mammals, females have two X chromosomes while males only have one X chromosome and one Y chromosome. X inactivation has evolved to randomly silence one of two Xs in female to balance the dosage of X-linked genes between the sexes. Although most genes on the inactive X are silenced, some genes escape from this silencing with expression from both the active and inactive X. In this dissertation, first, I performed a global survey of genes escaping from X inactivation by RNA sequencing in a mouse hybrid cell line. This finding showed that the mouse has few escape genes compared to human, which is consistent with the differences observed in phenotypes of mice and women with a single X chromosome – X0 mice have a near normal phenotype while 45, X women have Turner syndrome. H3K27me3, a repressive histone mark associated with the Xi is absent at most escape genes. However, for some escape gene, enrichment of this repressive modification varies between tissues and developmental stages suggesting that escape from X inactivation may be regulated in a tissue and developmental stage specific manner. Second, I examined the distribution of a set of AT-rich motifs identified to be unique to the eutherian X and found that they were depleted at escape genes, suggesting a role for these motifs in regulation of the X chromosome. Third, I discovered that two i&barbelow;nactive X&barbelow; C&barbelow;TCF c&barbelow;lusters (IXCCs) produce non-coding RNAs and showed that they are involved in the perinucleolar targeting and the maintenance of repressive chromatin structure of the inactive X chromosome (Xi). |
