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XACT, a long noncoding transcript coating the active X chromosome in human pluripotent cells

Abstract

X-chromosome inactivation (XCI) in mammals relies on XIST, a long noncoding transcript that coats and silences the X chromosome in cis. Here we report the discovery of a long noncoding RNA, XACT, that is expressed from and coats the active X chromosome specifically in human pluripotent cells. In the absence of XIST, XACT is expressed from both X chromosomes in humans but not in mice, suggesting a unique role for XACT in the control of human XCI initiation.

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Figure 1: Characterization of XACT, a long intergenic RNA that coats the active X chromosome in hESCs.
Figure 2: XACT coats both X chromosomes in hESCs not expressing XIST, and the expression of XACT is restricted to pluripotent cells.

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Acknowledgements

We thank members of our laboratory and M. Lalande for stimulating discussion and critical reading of the manuscript. The research leading to these results has received funding from the European Research Council (ERC) under the European Community's Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement 206875 and the INSERM (Avenir Program R0721HS).

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C.V. and C.H. performed the experiments. Y.L. and L.D. did the bioinformatic analysis of XACT conservation. N.O. and A.B.-G. provided the H9-MSC-iPS system. A.R. contributed to the bioinformatics analysis of the RNA-seq data. C.V. and C.R. conceived and designed the experiments, and wrote the manuscript.

Corresponding author

Correspondence to Claire Rougeulle.

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The authors declare no competing financial interests.

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Supplementary Methods and Supplementary Figures 1–6 (PDF 9036 kb)

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Vallot, C., Huret, C., Lesecque, Y. et al. XACT, a long noncoding transcript coating the active X chromosome in human pluripotent cells. Nat Genet 45, 239–241 (2013). https://doi.org/10.1038/ng.2530

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