YY1 Tethers Xist RNA to the Inactive X Nucleation Center

SummaryThe long noncoding Xist RNA inactivates one X chromosome in the female mammal. Current models posit that Xist induces silencing as it spreads along X and recruits Polycomb complexes. However, the mechanisms for Xist loading and spreading are currently unknown. Here, we define the nucleation center for Xist RNA and show that YY1 docks Xist particles onto the X chromosome. YY1 is a “bivalent” protein, capable of binding both RNA and DNA through different sequence motifs. Xist's exclusive attachment to the inactive X is determined by an epigenetically regulated trio of YY1 sites as well as allelic origin. Specific YY1-to-RNA and YY1-to-DNA contacts are required to load Xist particles onto X. YY1 interacts with Xist RNA through Repeat C. We propose that YY1 acts as adaptor between regulatory RNA and chromatin targets.

Graphical AbstractFigure optionsDownload high-quality image (237 K)Download as PowerPoint slideHighlights
► The inactive X nucleation center consists of three YY1 sites
► YY1 tethers Xist RNA to the nucleation center
► YY1 is bivalent, binding both RNA and DNA
► Xist RNA is diffusible and is trapped by the X chromosome via YY1