XACT Noncoding RNA Competes with XIST in the Control of X Chromosome Activity during Human Early Development

Publication date: Available online 15 December 2016
Source:Cell Stem Cell
Author(s): Céline Vallot, Catherine Patrat, Amanda J. Collier, Christophe Huret, Miguel Casanova, Tharvesh M. Liyakat Ali, Matteo Tosolini, Nelly Frydman, Edith Heard, Peter J. Rugg-Gunn, Claire Rougeulle
Sex chromosome dosage compensation is essential in most metazoans, but the developmental timing and underlying mechanisms vary significantly, even among placental mammals. Here we identify human-specific mechanisms regulating X chromosome activity in early embryonic development. Single-cell RNA sequencing and imaging revealed co-activation and accumulation of the long noncoding RNAs (lncRNAs) XACT and XIST on active X chromosomes in both early human pre-implantation embryos and naive human embryonic stem cells. In these contexts, the XIST RNA adopts an unusual, highly dispersed organization, which may explain why it does not trigger X chromosome inactivation at this stage. Functional studies in transgenic mouse cells show that XACT influences XIST accumulation in cis. Our findings therefore suggest a mechanism involving antagonistic activity of XIST and XACT in controlling X chromosome activity in early human embryos, and they highlight the contribution of rapidly evolving lncRNAs to species-specific developmental mechanisms.

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Teaser

Rougeulle and colleagues show that, in human pre-implantation embryos and naive human embryonic stem cells, the lncRNAs XIST and XACT accumulate together on active X chromosomes. Functional data suggest that XACT restrains XIST activity before the initiation of X inactivation takes place.


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