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Loda, Agnese; Brandsma, Johannes H; Vassilev, Ivaylo; Servant, Nicolas; Loos, Friedemann; Amirnasr, Azadeh; Splinter, Erik; Barillot, Emmanuel; Poot, Raymond A; Heard, Edith; Gribnau, Joost
Nature communications, 09/2017, Letnik: 8, Številka: 1Journal Article
Xist is indispensable for X chromosome inactivation. However, how Xist RNA directs chromosome-wide silencing and why some regions are more efficiently silenced than others remains unknown. Here, we explore the function of Xist by inducing ectopic Xist expression from multiple different X-linked and autosomal loci in mouse aneuploid and female diploid embryonic stem cells in which Xist-mediated silencing does not lead to lethal functional monosomy. We show that ectopic Xist expression faithfully recapitulates endogenous X chromosome inactivation from any location on the X chromosome, whereas long-range silencing of autosomal genes is less efficient. Long interspersed elements facilitate inactivation of genes located far away from the Xist transcription locus, and genes escaping X chromosome inactivation show enrichment of CTCF on X chromosomal but not autosomal loci. Our findings highlight important genomic and epigenetic features acquired during sex chromosome evolution to facilitate an efficient X chromosome inactivation process.Xist RNA is required for X chromosome inactivation but it is not well understood how Xist silences some regions more efficiently than others. Here, the authors induce ectopic Xist expression from multiple different X-linked and autosomal loci in cells to explore Xist function.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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