The Xist RNA-PRC2 complex at 20-nm resolution reveals a low Xist stoichiometry and suggests a hit-and-run mechanism in mouse cells

X-chromosome inactivation (XCI) is initiated by the long noncoding RNA Xist. Here we view Xist RNA and the Xi at 20-nm resolution using STochastic Optical Reconstruction Microscopy (STORM) and observe dynamics at the single-cell level not predicted by epigenomic analysis. Only 50-100 Xist molecules and ∼50 PRC2 foci are observed per Xi, contrasting with the chromosome-wide "coat" observed by deep sequencing and conventional microscopy. Xist knock-off experiments enable visualization of dissociation and relocalization dynamics, and support a functional tethering of Xist and PRC2. Thus, Xist-PRC2 complexes are less numerous than expected, implying that the Xist-PRC2 complexes methylate nucleosomes in a hit-and-run model.