XACT noncoding RNA competes with XIST in the control of X chromosome activity during human early development
2017
Vallot, Céline | Patrat, Catherine | Collier, Amanda J. | Huret, Christophe | Casanova, Miguel | Liyakat Ali, Tharvesh M. | Tosolini, Matteo | Frydman, Nelly | Heard, Edith | Rugg-Gunn, Peter J. | Rougeulle, Claire
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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