Jarid2 Is Implicated in the Initial Xist-Induced Targeting of PRC2 to the Inactive X Chromosome.
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.
Curie Institute, CNRS UMR3215, INSERM U934, 26 rue d'Ulm, Paris 75248, France.
Simão Teixeira
ST
da Rocha
Curie Institute, INSERM U900, Bioinformatics and Computational Systems Biology of Cancer, 26 rue d'Ulm, Paris 75248, France.
Valentina
V
Boeva
Curie Institute, CNRS UMR3215, INSERM U934, 26 rue d'Ulm, Paris 75248, France.
Martin
M
Escamilla-Del-Arenal
Curie Institute, CNRS UMR3215, INSERM U934, 26 rue d'Ulm, Paris 75248, France.
Katia
K
Ancelin
Curie Institute, CNRS UMR3215, INSERM U934, 26 rue d'Ulm, Paris 75248, France.
Camille
C
Granier
Curie Institute, CNRS UMR3215, INSERM U934, 26 rue d'Ulm, Paris 75248, France.
Neuza Reis
NR
Matias
Curie Institute, CNRS UMR3215, INSERM U934, 26 rue d'Ulm, Paris 75248, France.
Serena
S
Sanulli
Curie Institute, CNRS UMR3215, INSERM U934, 26 rue d'Ulm, Paris 75248, France.
Jen
J
Chow
Curie Institute, CNRS UMR3215, INSERM U934, 26 rue d'Ulm, Paris 75248, France.
Edda
E
Schulz
Curie Institute, CNRS UMR3215, INSERM U934, 26 rue d'Ulm, Paris 75248, France.
Christel
C
Picard
Howard Hughes Medical Institute, Department of Biochemistry, New York University School of Medicine, New York, NY 10016, USA.
Syuzo
S
Kaneko
Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen, Denmark.
Kristian
K
Helin
Howard Hughes Medical Institute, Department of Biochemistry, New York University School of Medicine, New York, NY 10016, USA.
Danny
D
Reinberg
Genomics, BioInnovationsZentrum, Technische Universität Dresden, Am Tatzberg 47-51, 01307 Dresden, Germany.
A Francis
AF
Stewart
Institute of Molecular Health Sciences, Swiss Federal Institute of Technology, ETH Zürich, Schafmattstrasse 22, 8049 Zurich.
Anton
A
Wutz
Curie Institute, CNRS UMR3215, INSERM U934, 26 rue d'Ulm, Paris 75248, France. Electronic address: raphael.margueron@curie.fr.
Raphaël
R
Margueron
Curie Institute, CNRS UMR3215, INSERM U934, 26 rue d'Ulm, Paris 75248, France. Electronic address: edith.heard@curie.fr.
Edith
E
Heard
D000818:Animals; D004303:Dosage Compensation, Genetic; D006801:Humans; D051379:Mice; D063151:Polycomb Repressive Complex 2 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D062085:RNA, Long Noncoding / Q000378:metabolism / Q000502:physiology*; D014960:X Chromosome / Q000378:metabolism*; D049951:X Chromosome Inactivation
C547777:JARID2 protein, human; D062085:RNA, Long Noncoding; C077885:XIST non-coding RNA; D063151:Polycomb Repressive Complex 2