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Cantone. J Transl Genet Genom 2017;1:1-14 Journal of Translational
DOI: 10.20517/jtgg.2017.19
Genetics and Genomics

www.jtggjournal.com
Topic: Reversing X Chromosome Inactivation as a New Therapeutic Treatment Open Access
for X-linked Diseases

Reversal of X chromosome inactivation:

lessons from pluripotent reprogramming of

mouse and human somatic cells

Irene Cantone

MRC London Institute of Medical Sciences (LMS), Imperial College of London, Hammersmith Hospital Campus, London W120NN, UK.

Correspondence to: Dr. Irene Cantone, MRC London Institute of Medical Sciences (LMS), Imperial College of London, Hammersmith Hospital
Campus, Du Cane road, London W120NN, UK. E-mail: irene.cantone81@gmail.com

How to cite this article: Cantone I. Reversal of X chromosome inactivation: lessons from pluripotent reprogramming of mouse and human somatic
cells. J Transl Genet Genom 2017;1:1-14.

ABSTRACT
Article history: X chromosome inactivation (XCI) is a strategy used by mammals to silence genes along one
Received: 12 Jul 2017 of the two female X chromosomes and equilibrate expression dosage between XY males and
First Decision: 26 Sep 2017 XX females. This epigenetically-inherited silencing is established during early embryonic
Revised: 26 Oct 2017 development and maintained thereafter through cell divisions. Seeding of multiple repressive
Accepted: 27 Oct 2017 epigenetic marks along the inactive X chromosome (Xi) makes inactivation extremely robust
Published: 16 Nov 2017 and difficult to reverse upon single genetic perturbations. Reversal of XCI has, however,
been observed when somatic cells are reprogrammed towards pluripotency, and in vitro
Key words: reprogramming techniques have been used in recent years to dissect Xi gene reactivation
X chromosome reactivation, mechanisms. These studies pave the way for developing novel therapeutic approaches for
pluripotent reprogramming, X-linked diseases. Here, the author reviews Xi reactivation during pluripotent reprogramming
X-linked disease
of mouse and human somatic cells, highlight recent advances and species-specific differences,
and discuss the relevance for human diseases.

INTRODUCTION to inactivate is completely random and, once
established in early embryonic precursors it is stably
Dosage compensation between XX females and XY maintained through cell divisions. As a consequence,
males is achieved in placental mammals by the random females are mosaics of cells expressing either the
inactivation of one of the two female X chromosomes [1,2] . maternal or paternal allele that co-exist in a 50:50 ratio.
This process - named X chromosome inactivation (XCI) Mosaicism makes females more refractory to diseases
- is a major example of epigenetic gene regulation that are caused by X-linked mutations because
that leads to global chromatin condensation and cells expressing the wild-type allele can functionally
transcriptional silencing along the future inactive X compensate the deficit in heterozygous carriers. In
chromosome (Xi) . The choice of which X chromosome addition, the X chromosome that carries mutations
[2]
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