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Mol Cell. 2018 May 3;70(3):462-472.e8. doi: 10.1016/j.molcel.2018.03.024.

The Ftx Noncoding Locus Controls X Chromosome Inactivation Independently of Its RNA Products.

Author information

1
Sorbonne Paris Cité, Epigenetics and Cell Fate, UMR 7216 CNRS, Université Paris Diderot, Paris, France.
2
Institut Curie, PSL Research University, CNRS, INSERM, UMR3215/U934 Genetics and Developmental Biology Unit, Mammalian Developmental Epigenetics Group, F-75005 Paris, France.
3
Institut Curie, PSL Research University, CNRS, INSERM, UMR3215/U934 Genetics and Developmental Biology Unit, Mammalian Developmental Epigenetics Group, F-75005 Paris, France; Department of Developmental Biology, Erasmus MC, Wytemaweg 80, 3015 CN Rotterdam, the Netherlands.
4
Sorbonne Paris Cité, Epigenetics and Cell Fate, UMR 7216 CNRS, Université Paris Diderot, Paris, France. Electronic address: celine.morey@univ-paris-diderot.fr.
5
Sorbonne Paris Cité, Epigenetics and Cell Fate, UMR 7216 CNRS, Université Paris Diderot, Paris, France. Electronic address: claire.rougeulle@univ-paris-diderot.fr.

Abstract

Accumulation of the Xist long noncoding RNA (lncRNA) on one X chromosome is the trigger for X chromosome inactivation (XCI) in female mammals. Xist expression, which needs to be tightly controlled, involves a cis-acting region, the X-inactivation center (Xic), containing many lncRNA genes that evolved concomitantly to Xist from protein-coding ancestors through pseudogeneization and loss of coding potential. Here, we uncover an essential role for the Xic-linked noncoding gene Ftx in the regulation of Xist expression. We show that Ftx is required in cis to promote Xist transcriptional activation and establishment of XCI. Importantly, we demonstrate that this function depends on Ftx transcription and not on the RNA products. Our findings illustrate the multiplicity of layers operating in the establishment of XCI and highlight the diversity in the modus operandi of the noncoding players.

KEYWORDS:

3D interactions; CTCF; X chromosome inactivation; long noncoding RNAs; mouse embryonic stem cell differentiation

PMID:
29706539
DOI:
10.1016/j.molcel.2018.03.024
[Indexed for MEDLINE]
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