In females, X chromosome inactivation (XCI) ensures transcriptional silencing of one of the two Xs (either in a random or imprinted fashion) in somatic cells. Comparing this silencing between species has offered insight into different mechanisms of X inactivation, providing clues into the evolution of this epigenetic process in mammals. Long-noncoding RNAs have emerged as a common theme in XCI of therian mammals (eutherian and marsupial). Eutherian X inactivation is regulated by the noncoding RNA product of XIST , within a cis -acting master control region called the X inactivation center (XIC). Marsupials XCI is XIST independent. Instead, XCI is controlled by the long-noncoding RNA Rsx , which appears to be a functional analog of the eutherian XIST gene, insofar that its transcript coats the inactive X and represses activity of genes in cis . In this review we discuss XCI in eutherians, and contrast imprinted X inactivation in mouse and marsupials. We provide particular focus on the evolution of genomic elements that confer the unique epigenetic features that characterize the inactive X chromosome.
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