Abstract
In female m ammals, 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.
Highlights
X chromosome inactivation (XCI) is the mechanism that has evolved in eutherian mammals to ensure dosage compensation between XX and XY individuals
This process is crucially dependent on a specific locus on the X — the X inactivation center (XIC) — which includes, among other genetic elements, the inactive X-specific transcript (Xist) gene, which is necessary for the process of XCI [1]
McHugh et al suggest that polycomb repressive complex 2 (PRC2) recruitment is a consequence of histone H3 deacetylation by Hdac3, part of the NCoR repressive complex, and exclusion of Pol RNA polymerase II (II) [23, 48]. They suggest that the silencing mediator for the retinoic acid receptor and thyroid hormone receptor/nuclear receptor co-repressor (SMRT/NCoR) complex is recruited to the inactivating X via SMRT- and HDAC-associated repressor complex/Msx2-interacting protein (SHARP/Spen), which itself directly binds to Xist RNA [23, 44] (Fig. 2b)
Summary
X chromosome inactivation (XCI) is the mechanism that has evolved in eutherian mammals to ensure dosage compensation between XX (female) and XY (male) individuals.
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