SPEN integrates transcriptional and epigenetic control of X-inactivation

@article{Dossin2020SPENIT,
  title={SPEN integrates transcriptional and epigenetic control of X-inactivation},
  author={François Dossin and Ines Pinheiro and Jan J. Żylicz and Julia Roensch and Samuel Collombet and Agn{\`e}s Le Saux and Tomasz Chelmicki and Mikael Attia and Varun Kapoor and Ye Zhan and Florent Dingli and Damarys Loew and Thomas Mercher and Job Dekker and Edith Heard},
  journal={Nature},
  year={2020},
  volume={578},
  pages={455 - 460}
}
Xist represents a paradigm for the function of long non-coding RNA in epigenetic regulation, although how it mediates X-chromosome inactivation (XCI) remains largely unexplained. Several proteins that bind to Xist RNA have recently been identified, including the transcriptional repressor SPEN 1 – 3 , the loss of which has been associated with deficient XCI at multiple loci 2 – 6 . Here we show in mice that SPEN is a key orchestrator of XCI in vivo and we elucidate its mechanism of action. We… Expand
SPEN is Required for Xist Upregulation during Initiation of X Chromosome Inactivation
TLDR
It is found that Xist-mediated SPEN recruitment to the Xi chromosome happens very early in XCI, and that SPEN-mediated silencing of the Tsix promoter is required for Xist upregulation, and failed XistUpregulation in Spen−/− ESCs can be rescued by concomitant removal of Tsix. Expand
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Spen links RNA-mediated endogenous retrovirus silencing and X chromosome inactivation
TLDR
It is shown that Spen, an Xist-binding repressor protein essential for XCI , binds to ancient retroviral RNA, performing a surveillance role to recruit chromatin silencing machinery to these parasitic loci. Expand
Spen links RNA-mediated endogenous retrovirus silencing and X chromosome inactivation
TLDR
Spen, an Xist-binding repressor protein essential for XCI3-7, binds to ancient retroviral RNA, performing a surveillance role to recruit chromatin silencing machinery to these parasitic loci, suggesting that insertion of an ERV element into proto-Xist may have been a critical evolutionary event. Expand
Xist drives spatial compartmentalization of DNA and protein to orchestrate initiation and maintenance of X inactivation.
TLDR
Recent work elucidating the role of Xist and its protein partners in mediating chromosome-wide transcriptional repression is reviewed, as well as a model by which Xist may compartmentalize proteins across the inactive X chromosome to enable both the initiation and maintenance of XCI. Expand
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TLDR
Here, the recent work focused on the role of Xist functional repeats and interacting RNA-binding factors in the establishment of the silent state of the X chromosome inactivation is reviewed. Expand
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TLDR
Recent work on establishing the transcriptional and chromatin kinetics of XCR are reviewed, as well as a model by which transcription factors mediate XCR not only via Xist repression, but also by direct targeting of X-linked genes is discussed. Expand
Elements at the 5′ end of Xist harbor SPEN-independent transcriptional antiterminator activity
TLDR
Xist requires sequence elements beyond its first two kilobases to robustly silence transcription, and the 5′ end of Xist harbors SPEN-independent transcriptional antiterminator activity that can repress proximal cleavage and polyadenylation. Expand
Elements at the 5′ end of Xist harbor SPEN-independent transcriptional antiterminator activity
TLDR
Xist requires sequence elements beyond its first two kilobases to robustly silence transcription, and the 5′ end of Xist harbors SPEN-independent transcriptional antiterminator activity that can repress proximal cleavage and polyadenylation. Expand
Progress toward understanding chromosome silencing by Xist RNA.
TLDR
Progress in understanding both how these pathways function in Xist-mediated silencing and the complex interplay between them are summarized. Expand
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