Xist nucleates local protein gradients to propagate silencing across the X chromosome

Abstract

Since publication of the original article, we have become aware of three errors in our paper that we are now correcting. (1) The author list omitted Joanna W. Jachowicz and Mackenzie Strehle. They contributed the initial observation that the intrinsically disordered region of SPEN is critical for silencing some genes on the X chromosome, and we are now including them as authors. The author list, affiliations, and author contributions have been updated online, and all co-authors have approved the changes. (2) We have added a new reference and citations to Jachowicz et al. ( 2021), which reports on how SPEN/SHARP mediates X-restricted, Xistdependent silencing. (3) In the "SMACs are the functional units of Xist-mediated XCI" section of the discussion, the molecular weight of SPEN was incorrectly reported as "500 KDa" instead of the correct value of "400 KDa" in the sentence "Each Xist-SMAC accumulates 35 copies of the 500 KDa protein SPEN." These changes have now been corrected online, and the authors apologize for any confusion.

LncRNAs in human cancers: signal from noise

“…Indeed, 75% of human long non-coding transcripts contain at least a partial retroviral insertion and thus repetitive sequences [24] that may naturally act as molecular crowders to rewire cellular compartmentalization in response to environmental cues. Such a model may solve the conservation and concentration paradox by explaining how stochastic events such as the aberrant expression of lncRNAs can give rise to conserved functions even at low concentrations [32] . Supporting this hypothesis, it was recently demonstrated that two copies of Xist, a lncRNA necessary for X inactivation in placental mammals and implicated in the development of haematological cancers in Mus musculus [33], are sufficient to enucleate 50 macromolecular foci, containing the critical silencing protein SPEN [32].…”

“…Such a model may solve the conservation and concentration paradox by explaining how stochastic events such as the aberrant expression of lncRNAs can give rise to conserved functions even at low concentrations [32] . Supporting this hypothesis, it was recently demonstrated that two copies of Xist, a lncRNA necessary for X inactivation in placental mammals and implicated in the development of haematological cancers in Mus musculus [33], are sufficient to enucleate 50 macromolecular foci, containing the critical silencing protein SPEN [32]. Overall, these observations suggest that a re-evaluation of the concepts of specificity and stoichiometry in RNA-protein interactions, may be necessary.…”

Systematic identification of cis-interacting lncRNAs and their targets

“…Even in low copy numbers, lncRNAs can initiate the formation of nuclear compartments by interacting with RBPs to regulate transcription [15]. LncRNAs are reported to form scaffolds with RBPs and other mediator proteins that regulate the process of transcription and chromatin remodeling [16][17][18].…”

LncRNA RUS shapes the gene expression program towards neurogenesis

“…LncRNA often work by recruiting epigenetic regulators to locally concentrate them at target chromatin (Markaki et al , 2021). Our RNA-affinity purification relies on protein- RUS interactions formed under physiological conditions in intact cells and purifying complexes under native conditions.…”