Evidence map›Paper›PMID 38759625›Full record

ArticleMolecular cell2024

G-quadruplex folding in Xist RNA antagonizes PRC2 activity for stepwise regulation of X chromosome inactivation.

Yong Woo Lee, Uri Weissbein, Roy Blum, Jeannie T Lee

Abstract read
In one paragraph

Article in Molecular cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Review
  9. HuRInterDB: A Database Exploring the Landscape of lncRNA-Protein Interactions.Computational and structural biotechnology journal · 2026
    Article
  10. Review
  11. Article
  12. Article
  13. Epstein-Barr Virus Encoded lncRNAs Control the Viral Lytic Switch.bioRxiv : the preprint server for biology · 2025
    Article
  14. Article
  15. Structural basis for the function of long noncoding RNAbioRxiv : the preprint server for biology · 2025
    Article
  16. Review
  17. Review
  18. Article
  19. Article
  20. Re-analysis of CLAP data affirms PRC2 as an RNA binding protein.bioRxiv : the preprint server for biology · 2025
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Yong Woo LeeDepartment of Molecular Biology, Massachusetts General Hospital and Department of Genetics, Harvard Medical School, Boston, MA 02114, USA.
Uri WeissbeinDepartment of Molecular Biology, Massachusetts General Hospital and Department of Genetics, Harvard Medical School, Boston, MA 02114, USA.
Roy BlumDepartment of Molecular Biology, Massachusetts General Hospital and Department of Genetics, Harvard Medical School, Boston, MA 02114, USA.
Jeannie T LeeDepartment of Molecular Biology, Massachusetts General Hospital and Department of Genetics, Harvard Medical School, Boston, MA 02114, USA. Electronic address: lee@molbio.mgh.harvard.edu.

Funding

Spreading of Xist RNA and Polycomb complexes along the inactive X-chromosome.R01HD097665 · NICHD · MASSACHUSETTS GENERAL HOSPITAL · PI LEE, JEANNIE T · 2019 to 2023
$3.5M
NICHD NIH HHS R01 HD097665
6 · The paper itself

Abstract

How Polycomb repressive complex 2 (PRC2) is regulated by RNA remains an unsolved problem. Although PRC2 binds G-tracts with the potential to form RNA G-quadruplexes (rG4s), whether rG4s fold extensively in vivo and whether PRC2 binds folded or unfolded rG4 are unknown. Using the X-inactivation model in mouse embryonic stem cells, here we identify multiple folded rG4s in Xist RNA and demonstrate that PRC2 preferentially binds folded rG4s. High-affinity rG4 binding inhibits PRC2's histone methyltransferase activity, and stabilizing rG4 in vivo antagonizes H3 at lysine 27 (H3K27me3) enrichment on the inactive X chromosome. Surprisingly, mutagenizing the rG4 does not affect PRC2 recruitment but promotes its release and catalytic activation on chromatin. H3K27me3 marks are misplaced, however, and gene silencing is compromised. Xist-PRC2 complexes become entrapped in the S1 chromosome compartment, precluding the required translocation into the S2 compartment. Thus, Xist rG4 folding controls PRC2 activity, H3K27me3 enrichment, and the stepwise regulation of chromosome-wide gene silencing.

Indexed as

G-QuadruplexesHistonesPolycomb Repressive Complex 2RNA, Long NoncodingX Chromosome InactivationAnimalsChromatinGene SilencingMiceMouse Embryonic Stem CellsProtein BindingRNA FoldingX ChromosomeChromatinHistonesPolycomb Repressive Complex 2RNA, Long NoncodingXIST non-coding RNAG4G-quadruplexesnoncoding RNAPolycomb repressive complex 2PRC2RNA structureX inactivationXist

Identifiers

PMID38759625
PMCPMC11505738

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.