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.

Additional Metadata
Persistent URL dx.doi.org/10.1038/s41467-017-00528-1, hdl.handle.net/1765/102144
Journal Nature Communications
Loda, A, Brandsma, J.H, Vassilev, I. (Ivaylo), Servant, N, Loos, F, Amirnasr, A. (Azadeh), … Gribnau, J.H. (2017). Genetic and epigenetic features direct differential efficiency of Xist-mediated silencing at X-chromosomal and autosomal locations. Nature Communications, 8(1). doi:10.1038/s41467-017-00528-1