Evidence map›Paper›PMID 21085182›Full record

ArticleNature2010

Molecular coupling of Tsix regulation and pluripotency.

Pablo Navarro, Andrew Oldfield, Julie Legoupi, Nicola Festuccia, Agnès Dubois, Mikael Attia, Jon Schoorlemmer, Claire Rougeulle, Ian Chambers, Philip Avner

Abstract read
PubMed Publisher
In one paragraph

Article in Nature, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers.

0numbers the graph read from it
0cells of the map it votes in
109citing papers in PubMed
11.8field-weighted citation impact, top 1% of its field
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

109 citing papers in PubMed, 207 citations in OpenAlex.

  1. Review
  2. Review
  3. Xist in X chromosome inactivation: mechanisms and disease relevance.Cell communication and signaling : CCS · 2025
    Review
  4. Article
  5. Article
  6. Review
  7. Insulation between adjacent TADs is controlled by the width of their boundaries through distinct mechanisms.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Cohesin controls X chromosome structure remodeling and X-reactivation during mouse iPSC-reprogramming.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  17. Long noncoding RNAGenes & diseases · 2022
    Review
  18. A long noncoding RNA influences the choice of the X chromosome to be inactivated.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  19. The Molecular and Nuclear Dynamics of X-Chromosome Inactivation.Cold Spring Harbor perspectives in biology · 2022
    Review
  20. Gene regulation in time and space during X-chromosome inactivation.Nature reviews. Molecular cell biology · 2022
    Review

49 more citing papers are in PubMed but not listed here.

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

10 authors at 5 institutions in 3 countries.

Pablo NavarroUnité de Génétique Moléculaire Murine, URA 2578, Institut Pasteur, 75724 Paris Cedex 15, France. pablo.navarro@ed.ac.uk
Andrew Oldfield
Julie Legoupi
Nicola Festuccia
Agnès Dubois
Mikael Attia
Jon Schoorlemmer
Claire Rougeulle
Ian Chambers
Philip Avner
Institut Pasteur · FRCentre National de la Recherche Scientifique · FRMedical Research Council · GBInstituto Aragonés de Ciencias de la Salud · ESUniversity of Edinburgh · GB

Funding

Wellcome Trust
6 · The paper itself

Abstract

The reprogramming of X-chromosome inactivation during the acquisition of pluripotency in vivo and in vitro is accompanied by the repression of Xist, the trigger of X-inactivation, and the upregulation of its antisense counterpart Tsix. We have shown that key factors supporting pluripotency-Nanog, Oct4 and Sox2-bind within Xist intron 1 in undifferentiated embryonic stem cells (ESC) to repress Xist transcription. However, the relationship between transcription factors of the pluripotency network and Tsix regulation has remained unclear. Here we show that Tsix upregulation in embryonic stem cells depends on the recruitment of the pluripotent marker Rex1, and of the reprogramming-associated factors Klf4 and c-Myc, by the DXPas34 minisatellite associated with the Tsix promoter. Upon deletion of DXPas34, binding of the three factors is abrogated and the transcriptional machinery is no longer efficiently recruited to the Tsix promoter. Additional analyses including knockdown experiments further demonstrate that Rex1 is critically important for efficient transcription elongation of Tsix. Hence, distinct embryonic-stem-cell-specific complexes couple X-inactivation reprogramming and pluripotency, with Nanog, Oct4 and Sox2 repressing Xist to facilitate the reactivation of the inactive X, and Klf4, c-Myc and Rex1 activating Tsix to remodel Xist chromatin and ensure random X-inactivation upon differentiation. The holistic pattern of Xist/Tsix regulation by pluripotent factors that we have identified suggests a general direct governance of complex epigenetic processes by the machinery dedicated to pluripotency.

Indexed as

AnimalsEmbryonic Stem CellsFemaleHomeodomain ProteinsKruppel-Like Factor 4Kruppel-Like Transcription FactorsMaleMiceMinisatellite RepeatsNanog Homeobox ProteinOctamer Transcription Factor-3Pluripotent Stem CellsPromoter Regions, GeneticProto-Oncogene Proteins c-mycRNA, Long NoncodingRNA, UntranslatedHomeodomain ProteinsKlf4 protein, mouseKruppel-Like Factor 4Kruppel-Like Transcription FactorsMyc protein, mouseNanog Homeobox ProteinNanog protein, mouseOctamer Transcription Factor-3Pou5f1 protein, mouseProto-Oncogene Proteins c-mycRNA, Long NoncodingRNA, UntranslatedSox2 protein, mouseSOXB1 Transcription FactorsTranscription FactorsTsix transcript, mouseXIST non-coding RNAZfp42 protein, mouse

Identifiers

PMID21085182
OpenAlexW1967867693

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.