A prominent and conserved role for YY1 in Xist transcriptional activation
Ouimette et al. Epigenetics & Chromatin
A prominent and conserved role for YY1 in Xist transcriptional activation
Jean-Francois Ouimette 1 2
Mlanie Makhlouf 1 2
Andrew Oldfield 1 2
Pablo Navarro 0
Claire Rougeulle 1 2
0 MRC Centre for Regenerative Medicine, School of Biological Sciences, University of Edinburgh , 5 Little France Drive, Edinburgh EH164UU, Scotland , UK
1 Paris Diderot University , Sorbonne Paris Cite, F-75013 Paris , France
2 CNRS, UMR7216 Epigenetics and Cell Fate , F-75013 Paris , France
2013 Ouimette et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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From Epigenetics and Chromatin: Interactions and processes
Boston, MA, USA. 11-13 March 2013
Dosage compensation for X-linked genes in female
mammals relies on X-chromosome inactivation. This process
involves monoallelic up-regulation of the non-coding Xist
RNA which coats in cis the chromosome and triggers
epigenetic reprogramming that will prevent
chromosomewide transcription. Xist transcription is controlled, directly
and/or indirectly, by several ncRNA (Tsix, Jpx, Ftx) and
factors (Sox2, Oct4, Nanog, Rex1, Rnf12). However,
mechanisms leading to Xist monoallelic regulation remain
poorly understood.
Using mouse ES and differentiating cells, we identified
specific YY1 and CTCF interacting sites on the Xist locus
of the inactive X-chromosome. We show that this
monoallelic binding is controlled by DNA methylation. To gain
further insights into YY1 functional role on the Xist locus,
we conducted YY1 knockdown experiments. We show by
RNA-FISH that depletion of YY1 in female somatic cells
impairs the accumulation of Xist on the inactive
X-chromosome. This is likely due to a transcriptional effect as we
observe a drastic reduction of both spliced and unspliced
Xist RNA levels. This hypothesis is further reinforced by
the in vitro analysis Xist promoter activity, which displays
strict dependency on the YY1 binding sites. Importantly,
YY1 is also necessary for the upregulation of Xist that
triggers X-chromosome inactivation. Taken together, these
results suggest a strong requirement for YY1 in the
upregulation and maintenance of Xist transcription.
Importantly, we demonstrate that the function of YY1 in the
control of Xist expression is conserved in humans and
predicted in other mammalian species.
These results highlight the importance of YY1 both in
the monoallelic upregulation of Xist at the exit of
pluripotency and in the maintenance of its expression in somatic
cells. Taken together with previous studies, we propose
1CNRS, UMR7216 Epigenetics and Cell Fate, F-75013 Paris, France
Full list of author information is available at the end of the article
that through its dual action on Tsix and Xist, YY1 acts as
a bimodal transcriptional regulator of X-inactivation.
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