| First Author | Pandya-Jones A | Year | 2020 |
| Journal | Nature | Volume | 587 |
| Issue | 7832 | Pages | 145-151 |
| PubMed ID | 32908311 | Mgi Jnum | J:297416 |
| Mgi Id | MGI:6472600 | Doi | 10.1038/s41586-020-2703-0 |
| Citation | Pandya-Jones A, et al. (2020) A protein assembly mediates Xist localization and gene silencing. Nature 587(7832):145-151 |
| abstractText | Nuclear compartments have diverse roles in regulating gene expression, yet the molecular forces and components that drive compartment formation remain largely unclear(1). The long non-coding RNA Xist establishes an intra-chromosomal compartment by localizing at a high concentration in a territory spatially close to its transcription locus(2) and binding diverse proteins(3-5) to achieve X-chromosome inactivation (XCI)(6,7). The XCI process therefore serves as a paradigm for understanding how RNA-mediated recruitment of various proteins induces a functional compartment. The properties of the inactive X (Xi)-compartment are known to change over time, because after initial Xist spreading and transcriptional shutoff a state is reached in which gene silencing remains stable even if Xist is turned off(8). Here we show that the Xist RNA-binding proteins PTBP1(9), MATR3(10), TDP-43(11) and CELF1(12) assemble on the multivalent E-repeat element of Xist(7) and, via self-aggregation and heterotypic protein-protein interactions, form a condensate(1) in the Xi. This condensate is required for gene silencing and for the anchoring of Xist to the Xi territory, and can be sustained in the absence of Xist. Notably, these E-repeat-binding proteins become essential coincident with transition to the Xist-independent XCI phase(8), indicating that the condensate seeded by the E-repeat underlies the developmental switch from Xist-dependence to Xist-independence. Taken together, our data show that Xist forms the Xi compartment by seeding a heteromeric condensate that consists of ubiquitous RNA-binding proteins, revealing an unanticipated mechanism for heritable gene silencing. |
