Xist Deletional Analysis Reveals an Interdependency between Xist RNA and Polycomb Complexes for Spreading along the Inactive X.
Mol Cell
; 74(1): 101-117.e10, 2019 04 04.
Article
in En
| MEDLINE
| ID: mdl-30827740
ABSTRACT
During X-inactivation, Xist RNA spreads along an entire chromosome to establish silencing. However, the mechanism and functional RNA elements involved in spreading remain undefined. By performing a comprehensive endogenous Xist deletion screen, we identify Repeat B as crucial for spreading Xist and maintaining Polycomb repressive complexes 1 and 2 (PRC1/PRC2) along the inactive X (Xi). Unexpectedly, spreading of these three factors is inextricably linked. Deleting Repeat B or its direct binding partner, HNRNPK, compromises recruitment of PRC1 and PRC2. In turn, ablating PRC1 or PRC2 impairs Xist spreading. Therefore, Xist and Polycomb complexes require each other to propagate along the Xi, suggesting a positive feedback mechanism between RNA initiator and protein effectors. Perturbing Xist/Polycomb spreading causes failure of de novo Xi silencing, with partial compensatory downregulation of the active X, and also disrupts topological Xi reconfiguration. Thus, Repeat B is a multifunctional element that integrates interdependent Xist/Polycomb spreading, silencing, and changes in chromosome architecture.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
X Chromosome
/
Gene Deletion
/
Gene Silencing
/
X Chromosome Inactivation
/
Fibroblasts
/
Polycomb Repressive Complex 1
/
Polycomb Repressive Complex 2
/
RNA, Long Noncoding
/
Mouse Embryonic Stem Cells
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Mol Cell
Journal subject:
BIOLOGIA MOLECULAR
Year:
2019
Type:
Article
Affiliation country:
United States