Epigenetics of X-chromosome Inactivation

X-chromosome inactivation (XCI) evolved as a complex and multi-layered epigenetic mechanism to enable dosage equivalence for X-linked genes expression between XX and XY individuals in marsupial and placental mammals. Nevertheless, not all X-linked genes are entirely inactivated and their expression from the inactive X-chromosome may underlie sex differences between females and males. Besides, XCI statuses can epigenetically modify the inheritance mode of X-driven phenotypes and contribute to variability of human conditions. On the other hand, by taking advantage of the natural plasticity of XCI, induced reactivation of the Xi may represent a hopeful strategy for treating dominant X-linked conditions in affected females. This chapter provides an overview of XCI based on the main epigenetic regulatory events involved and the e(X)ceptional features of XCI on health and diseases.