Xist localization and function: new insights from multiple levels.
In female mammals, one of the two X chromosomes in each cell is transcriptionally silenced in order to achieve dosage compensation between the genders in a process called X chromosome inactivation. The master regulator of this process is the long non-coding RNA Xist. During X-inactivation, Xist accumulates in cis on the future inactive X chromosome, triggering a cascade of events that provoke the stable silencing of the entire chromosome, with relatively few genes remaining active. How Xist spreads, what are its binding sites, how it recruits silencing factors and how it induces a specific topological and nuclear organization of the chromatin all remain largely unanswered questions. Recent studies have improved our understanding of Xist localization and the proteins with which it interacts, allowing a reappraisal of ideas about Xist function. We discuss recent advances in our knowledge of Xist-mediated silencing, focusing on Xist spreading, the nuclear organization of the inactive X chromosome, recruitment of the polycomb complex and the role of the nuclear matrix in the process of X chromosome inactivation.
EMBL Mouse Biology Unit, Monterotondo, 00015 (RM), Italy. andrea.cerase@embl.it.
Andrea
A
Cerase
Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK.
Greta
G
Pintacuda
Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK.
Anna
A
Tattermusch
EMBL Mouse Biology Unit, Monterotondo, 00015 (RM), Italy. phil.avner@embl.it.|Institut Pasteur, Unite de Genetique Moleculaire Murine, CNRS, URA2578, Paris, France. phil.avner@embl.it.
Philip
P
Avner
D000818:Animals; D002467:Cell Nucleus / Q000235:genetics; D005260:Female; D020868:Gene Silencing; D051379:Mice; D063146:Polycomb-Group Proteins / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000032:analysis / Q000378:metabolism*; D049951:X Chromosome Inactivation
D063146:Polycomb-Group Proteins; D062085:RNA, Long Noncoding; C077885:XIST non-coding RNA