Abstract
In mammals, the genic disequilibrium between males (XY) and females (XX) is resolved through the inactivation of one of the X-chromosomes in females. X-chromosome inactivation (XCI) takes place in all mammalian species, but has mainly been studied in the mouse model where it was shown to be controlled by the interplay of several long non-coding RNA (lncRNA). However, recent data point toward the existence of species divergences among mammals in the strategies used to achieve XCI. The recent discovery of XACT, a novel lncRNA that coats the active X-chromosome specifically in human pluripotent cells, further highlights the existence of human-specific mechanisms of X-chromosome regulation. Here, we discuss the roles of lncRNAs in defining species-specific mechanisms controlling X-inactivation and explore the potential role of large lncRNAs in gene activation.