A prominent and conserved role for YY1 in Xist transcriptional activation

Epigenetics & Chromatin, Mar 2013

Jean-Francois Ouimette, Mélanie Makhlouf, Andrew Oldfield, Pablo Navarro, Claire Rougeulle

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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. - 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. Submit your next manuscript to BioMed Central and take full advantage of: Submit your manuscript at www.biomedcentral.com/submit (...truncated)


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Jean-Francois Ouimette, Mélanie Makhlouf, Andrew Oldfield, Pablo Navarro, Claire Rougeulle. A prominent and conserved role for YY1 in Xist transcriptional activation, Epigenetics & Chromatin, 2013, pp. P62, 6,