Review Paper

Human Genetics

, Volume 130, Issue 2, pp 223-236

First online:

Open Access This content is freely available online to anyone, anywhere at any time.

Xist regulation and function eXplored

  • Daphne B. PontierAffiliated withDepartment of Reproduction and Development, Erasmus MC
  • , Joost GribnauAffiliated withDepartment of Reproduction and Development, Erasmus MC Email author 


X chromosome inactivation (XCI) is a process in mammals that ensures equal transcript levels between males and females by genetic inactivation of one of the two X chromosomes in females. Central to XCI is the long non-coding RNA Xist, which is highly and specifically expressed from the inactive X chromosome. Xist covers the X chromosome in cis and triggers genetic silencing, but its working mechanism remains elusive. Here, we review current knowledge about Xist regulation, structure, function and conservation and speculate on possible mechanisms by which its action is restricted in cis. We also discuss dosage compensation mechanisms other than XCI and how knowledge from invertebrate species may help to provide a better understanding of the mechanisms of mammalian XCI.