4.4 Review

The tandem repeat modules of Xist lncRNA : a swiss army knife for the control of X-chromosome inactivation

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Summary: Dosage compensation of X-linked gene expression in female eutherian mammals is achieved through transcriptional silencing of one X chromosome. X chromosome inactivation (XCI) is dependent on Xist, a long noncoding RNA that coats and silences the X chromosome. XCI has emerged as a paradigm for studying crucial nuclear processes and their functional interplay.

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Summary: The lncRNA Xist forms locally confined foci containing a small number of RNA molecules and supramolecular complexes with critical silencing protein SPEN. Protein aggregation and exchange generate local gradients that regulate broad chromatin regions and propagate gene silencing. This mechanism involves functional nuclear compartmentalization through crowding of regulators, enabling silencing of target genes by few RNA molecules.
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Summary: Silencing most gene expression from all but one X chromosome in female mammals is crucial for overcoming X-linked gene expression imbalances with males, with the long non-coding RNA XIST playing a central role in establishing gene silencing on the inactivated X chromosome. Knocking out XIST expression from the inactive X chromosome in human somatic cells led to limited changes in heterochromatin features, indicating maintenance of dosage compensation at the Xi involving multiple redundant layers of gene silencing.

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Summary: The study reveals that Xist RNA directs X chromosome inactivation in mammals by spreading along the chromosome and recruiting chromatin modifiers, with a feedback mechanism linking Xist RNA synthesis and degradation, as well as physical coupling between preceding and newly synthesized Xist RNA molecules. SPEN, a key factor for Xist-mediated gene silencing, plays a distinct role in Xist RNA localization, stability, and coupling behaviors.

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