1 Helin Group, BRIC Research Groups, BRIC, Københavns Universitet2 Administration, BRIC Administration, BRIC, Københavns Universitet3 Curie Institute, CNRS UMR3215, INSERM U934, 26 rue d'Ulm, Paris 75248, France.4 Curie Institute, INSERM U900, Bioinformatics and Computational Systems Biology of Cancer, 26 rue d'Ulm, Paris 75248, France.5 Howard Hughes Medical Institute, Department of Biochemistry, New York University School of Medicine, New York, NY 10016, USA.6 BRIC Administration, BRIC, Faculty of Health and Medical Sciences, Københavns Universitet7 Genomics, BioInnovationsZentrum, Technische Universität Dresden, Am Tatzberg 47-51, 01307 Dresden, Germany.8 Institute of Molecular Health Sciences, Swiss Federal Institute of Technology, ETH Zürich, Schafmattstrasse 22, 8049 Zurich.9 Curie Institute, CNRS UMR3215, INSERM U934, 26 rue d'Ulm, Paris 75248, France. Electronic address: email@example.com Curie Institute, CNRS UMR3215, INSERM U934, 26 rue d'Ulm, Paris 75248, France. Electronic address: firstname.lastname@example.org BRIC Administration, BRIC, Faculty of Health and Medical Sciences, Københavns Universitet
During X chromosome inactivation (XCI), the Polycomb Repressive Complex 2 (PRC2) is thought to participate in the early maintenance of the inactive state. Although Xist RNA is essential for the recruitment of PRC2 to the X chromosome, the precise mechanism remains unclear. Here, we demonstrate that the PRC2 cofactor Jarid2 is an important mediator of Xist-induced PRC2 targeting. The region containing the conserved B and F repeats of Xist is critical for Jarid2 recruitment via its unique N-terminal domain. Xist-induced Jarid2 recruitment occurs chromosome-wide independently of a functional PRC2 complex, unlike at other parts of the genome, such as CG-rich regions, where Jarid2 and PRC2 binding are interdependent. Conversely, we show that Jarid2 loss prevents efficient PRC2 and H3K27me3 enrichment to Xist-coated chromatin. Jarid2 thus represents an important intermediate between PRC2 and Xist RNA for the initial targeting of the PRC2 complex to the X chromosome during onset of XCI.