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Przanowski et al. J Transl Genet Genom 2018;2:2 Journal of Translational
DOI: 10.20517/jtgg.2017.03 Genetics and Genomics

Review Open Access

Novel molecular players of X chromosome
inactivation: new technologies and new insights

Piotr Przanowski*, Urszula Waśko*, Sanchita Bhatnagar
Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
*Authors contributed equally.

Correspondence to: Dr. Sanchita Bhatnagar, Department of Biochemistry and Molecular Genetics, University of Virginia School
of Medicine, 1340 Jefferson Park Ave, Pinn Hall 6044, Charlottesville, VA 22908, USA. E-mail: sb5fk@virginia.edu
How to cite this article: Przanowski P, Waśko U, Bhatnagar S. Novel molecular players of X chromosome inactivation: new
technologies and new insights. J Transl Genet Genom 2018;2:2. http://dx.doi.org/10.20517/jtgg.2017.03
Received: 29 Nov 2017 First Decision: 22 Jan 2018 Revised: 8 Feb 2018 Accepted: 10 Feb 2018 Published: 27 Feb 2018

Science Editor: Andrea Cerase Copy Editor: Jun-Yao Li Production Editor: Cai-Hong Wang

Abstract
The dosage compensation in placental mammals is achieved by silencing of one copy of the X chromosomes in a female
cell by a process called X chromosome inactivation (XCI). XCI ensures equal gene dosage for X-linked genes between the
two genders. Although the choice of X chromosome to be silenced is random, once the silencing of the X chromosome has
been established, this process is highly regulated and maintained throughout subsequent cell divisions. A long non-coding
RNA, Xist, and its interacting proteins execute this multistep process, but several of these regulatory proteins remain
unidentified. Recent technological advances based on the genetic and proteomics screening have identified several new
regulatory factors as well as dissected the molecular details of XCI regulation. Moreover, identification of regulators of XCI
offers an opportunity to explore reactivation of the inactive X chromosome (Xi) as a potential therapeutic strategy to treat
X-linked diseases, like Rett syndrome. Here, we summarize recent reports that identified new regulatory proteins and RNA
species playing a crucial role in Xist localization and spreading, recruitment of silencing machinery to the Xi, Xist interaction
with chromatin, and structural organization of the Xi in the nuclei.

Keywords: X chromosome inactivation, X chromosome reactivation, inactive X chromosome, X chromosome inactivation factor,
Xist

INTRODUCTION
X chromosome inactivation (XCI) is an epigenetic silencing phenomenon that achieves dosage compensation
in mammals. First described by Lyon in 1961, XCI is established during early embryonic development,
[1]
and the fixed inactivation is then inherited through subsequent divisions in somatic cells. Ultimately, XCI

© The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0
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