Details

Autor(en) / Beteiligte

• Pandya-Jones, Amy
• Markaki, Yolanda
• Serizay, Jacques
• Chitiashvili, Tsotne
• Mancia Leon, Walter R.
• Damianov, Andrey
• Chronis, Constantinos
• Papp, Bernadett
• Chen, Chun-Kan
• McKee, Robin
• Wang, Xiao-Jun
• Chau, Anthony
• Sabri, Shan
• Leonhardt, Heinrich
• Zheng, Sika
• Guttman, Mitchell
• Black, Douglas. L.
• Plath, Kathrin

Titel

A protein assembly mediates Xist localization and gene silencing

Ist Teil von

• Nature (London), 2020-11, Vol.587 (7832), p.145-151

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. A protein condensate formed by multivalent interactions between the long non-coding RNA Xist and specific RNA-binding proteins drives the compartmentalization required to perpetuate gene silencing on the inactive X chromosome.