The Matrix Protein hnRNP U Is Required for Chromosomal Localization of Xist RNA

SummaryIn XX female mammals, one of the two X chromosomes is epigenetically inactivated to equalize gene expression with XY males. The formation of the inactive X chromosome (Xi) is regulated by an X-linked long noncoding RNA Xist, which accumulates on the entire length of the chromosome in cis and induces heterochromatin formation. However, the mechanism by which Xist RNA “paints” the Xi has long remained elusive. Here, we show that a matrix protein hnRNP U/SP120/SAF-A is required for the accumulation of Xist RNA on the Xi. Xist RNA and hnRNP U interact and upon depletion of hnRNP U, Xist RNA is detached from the Xi and diffusely localized into the nucleoplasm. In addition, ES cells lacking hnRNP U expression fail to form the Xi. We propose that the association with matrix proteins is an essential step in the epigenetic regulation of gene expression by Xist RNA.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (203 K)Download as PowerPoint slideHighlights► Screening of siRNA library identifies hnRNP U as a Xist-localizing factor ► hnRNP U directly interacts with Xist via its RNA-binding domain ► Both matrix- and RNA-binding domains are required for the Xist localization ► hnRNP U is essential for establishment of the inactive X chromosome