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Mol Cell. 2014 Jan 23;53(2):301-16. doi: 10.1016/j.molcel.2014.01.002.

Jarid2 Is Implicated in the Initial Xist-Induced Targeting of PRC2 to the Inactive X Chromosome.

Author information

  • 1Curie Institute, CNRS UMR3215, INSERM U934, 26 rue d'Ulm, Paris 75248, France.
  • 2Curie Institute, INSERM U900, Bioinformatics and Computational Systems Biology of Cancer, 26 rue d'Ulm, Paris 75248, France.
  • 3Howard Hughes Medical Institute, Department of Biochemistry, New York University School of Medicine, New York, NY 10016, USA.
  • 4Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen, Denmark.
  • 5Genomics, BioInnovationsZentrum, Technische Universität Dresden, Am Tatzberg 47-51, 01307 Dresden, Germany.
  • 6Institute of Molecular Health Sciences, Swiss Federal Institute of Technology, ETH Zürich, Schafmattstrasse 22, 8049 Zurich.
  • 7Curie Institute, CNRS UMR3215, INSERM U934, 26 rue d'Ulm, Paris 75248, France. Electronic address: raphael.margueron@curie.fr.
  • 8Curie Institute, CNRS UMR3215, INSERM U934, 26 rue d'Ulm, Paris 75248, France. Electronic address: edith.heard@curie.fr.

Abstract

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.

PMID:
24462204
DOI:
10.1016/j.molcel.2014.01.002
[PubMed - indexed for MEDLINE]
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