Have humans lost control: The elusive X-controlling element

Semin Cell Dev Biol. 2016 Aug;56:71-77. doi: 10.1016/j.semcdb.2016.01.044. Epub 2016 Feb 3.


The process of X-chromosome inactivation (XCI) randomly silences one of two X chromosomes in normal female cells. The ability to predict if there is a preference for one of the two Xs to be chosen (and survive) more often as the active X has important repercussions in human health and X-linked disease. Mice have a genetic component that modulates non-random skewing called the X-controlling element (Xce). Although the nature of the locus and its mechanisms of action are still under investigation, it is clear that different mouse strains carry unique Xce alleles on their X chromosomes, resulting in distinct skewing phenotypes in the F1 progeny of hybrid crosses. Whether a similar mechanism exists in humans is unclear, and challenges to identifying such a locus include the complexity and diversity of the human genome, the restricted time points and tissue(s) of examination in human subjects, and the lack of a model system recapitulating XCI in early development. In this review we consider the evidence for such a controlling locus in humans, in addition to discussing if we have the power to recognize it given the contribution of selective growth in causing skewed patterns of XCI.

Keywords: Dosage compensation; Mosaicism; Skewing; X inactivation center; X-chromosome inactivation; X-controlling element.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Genetic Loci
  • Humans
  • Models, Biological
  • X Chromosome / genetics*
  • X Chromosome Inactivation / genetics