XACT Noncoding RNA Competes with XIST in the Control of X Chromosome Activity during Human Early Development.
Research paper by
Céline C Vallot, Catherine C Patrat, Amanda J AJ Collier, Christophe C Huret, Miguel M Casanova, Tharvesh M TM Liyakat Ali, Matteo M Tosolini, Nelly N Frydman, Edith E Heard, Peter J PJ Rugg-Gunn, Claire C 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.