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. [Display omitted] •Jarid2 is required for efficient PRC2 recruitment to the inactive X chromosome•Xist-induced recruitment of Jarid2 is independent of a functional PRC2•Xist-induced PRC2 recruitment obeys different rules from the rest of the genome•Repeats B and F of Xist RNA are required for Jarid2/PRC2 recruitment How PRC2 is recruited to the inactive X chromosome is unclear. Rocha et al. show that Jarid2, a PRC2 cofactor, is required for efficient chromosome-wide PRC2 recruitment in a manner that depends upon the B and F repeats of Xist RNA.