Researchers have discovered new insights into how one of the two X-chromosomes is silenced during the development of female human embryos and also in lab-grown stem cells. X-chromosome silencing is essential for proper development and these new findings are important for understanding how the activity of the X-chromosome is regulated to ensure the healthy development of human embryos. Female cells have two X-chromosomes. One X-chromosome is shut down in the earliest stages of development preventing the duplicated expression of genes from both X-chromosomes. Previous work using mouse embryos showed that a long RNA molecule called Xist coats regions of the silenced X-chromosome. By latching on to the DNA, Xist recruits proteins that shut down the chromosome. However, although XIST is expressed in human embryos, X-chromosome silencing isn't triggered until a few days later. The different observation in mouse and human embryos suggests that XIST is unable to fulfil the same role in humans as in mouse development. Until now, it was unclear why XIST does not inactivate the X-chromosome in human embryos, or what triggers X-chromosome silencing. Researchers at the Paris Diderot University, Institut Curie, and the Babraham Institute reported on December 15, 2016 in Cell Stem Cell that a second long RNA molecule, XACT, which exists in humans but not in mice, accumulates with XIST on active X-chromosomes in human embryos. The two RNAs do not overlap; instead XACT and XIST occupy large and distinct territories on the X-chromosome. Strikingly, unspecialized “naïve” human embryonic stem cells show the same pattern of XACT and XIST accumulation on active X-chromosomes, which suggests that this important epigenetic feature of embryo development is conserved in stem cells cultured in the laboratory.
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