Evidence map›Paper›PMID 26429547›Full record

ArticleGenome biology2015

Impact of flanking chromosomal sequences on localization and silencing by the human non-coding RNA XIST.

Angela D Kelsey, Christine Yang, Danny Leung, Jakub Minks, Thomas Dixon-McDougall, Sarah E L Baldry, Aaron B Bogutz, Louis Lefebvre, Carolyn J Brown

Open access · goldAbstract read
In one paragraph

Article in Genome biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
1.4field-weighted citation impact, top 20% 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

34 citing papers in PubMed, 47 citations in OpenAlex.

  1. Article
  2. Genome research · 2025
    Article
  3. eLife · 2025
    Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Modeling specific aneuploidies: from karyotype manipulations to biological insights.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2023
    Review
  11. Article
  12. Gene regulation in time and space during X-chromosome inactivation.Nature reviews. Molecular cell biology · 2022
    Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Epigenetics and sarcoidosis.European respiratory review : an official journal of the European Respiratory Society · 2021
    Review
  18. Revisiting the consequences of deleting the X inactivation center.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  19. Decoding LncRNAs.Cancers · 2021
    Review
  20. Review
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

9 authors at 2 institutions in 4 countries.

Angela D KelseyDepartment of Medical Genetics, Molecular Epigenetics Group, Life Sciences Institute, University of British Columbia, Vancouver, Canada. adkelsey1@gmail.com.
Christine YangDepartment of Medical Genetics, Molecular Epigenetics Group, Life Sciences Institute, University of British Columbia, Vancouver, Canada. yoyo.rolls@gmail.com.
Danny LeungLudwig Institute for Cancer Research, University of California at San Diego School of Medicine, La Jolla, CA, USA. dcyleung@ust.hk.
Jakub MinksDepartment of Medical Genetics, Molecular Epigenetics Group, Life Sciences Institute, University of British Columbia, Vancouver, Canada. jakub.minks@gmail.com.
Thomas Dixon-McDougallDepartment of Medical Genetics, Molecular Epigenetics Group, Life Sciences Institute, University of British Columbia, Vancouver, Canada. tom.dixon.mcdougall@alumni.ubc.ca.
Sarah E L BaldryDepartment of Medical Genetics, Molecular Epigenetics Group, Life Sciences Institute, University of British Columbia, Vancouver, Canada. sbaldry@mail.ubc.ca.
Aaron B BogutzDepartment of Medical Genetics, Molecular Epigenetics Group, Life Sciences Institute, University of British Columbia, Vancouver, Canada. aaron.bogutz@ubc.ca.
Louis LefebvreDepartment of Medical Genetics, Molecular Epigenetics Group, Life Sciences Institute, University of British Columbia, Vancouver, Canada. louis.lefebvre@ubc.ca.
Carolyn J BrownDepartment of Medical Genetics, Molecular Epigenetics Group, Life Sciences Institute, University of British Columbia, Vancouver, Canada. Carolyn.Brown@UBC.Ca.
University of British Columbia · CALudwig Cancer Research · BE

Funding

Canadian Institutes of Health Research MOP-119357Canadian Institutes of Health Research MOP-13680
6 · The paper itself

Abstract

backgroundX-chromosome inactivation is a striking example of epigenetic silencing in which expression of the long non-coding RNA XIST initiates the heterochromatinization and silencing of one of the pair of X chromosomes in mammalian females. To understand how the RNA can establish silencing across millions of basepairs of DNA we have modelled the process by inducing expression of XIST from nine different locations in human HT1080 cells.

resultsLocalization of XIST, depletion of Cot-1 RNA, perinuclear localization, and ubiquitination of H2A occurs at all sites examined, while recruitment of H3K9me3 was not observed. Recruitment of the heterochromatic features SMCHD1, macroH2A, H3K27me3, and H4K20me1 occurs independently of each other in an integration site-dependent manner. Silencing of flanking reporter genes occurs at all sites, but the spread of silencing to flanking endogenous human genes is variable in extent of silencing as well as extent of spread, with silencing able to skip regions. The spread of H3K27me3 and loss of H3K27ac correlates with the pre-existing levels of the modifications, and overall the extent of silencing correlates with the ability to recruit additional heterochromatic features.

conclusionsThe non-coding RNA XIST functions as a cis-acting silencer when expressed from nine different locations throughout the genome. A hierarchy among the features of heterochromatin reveals the importance of interaction with the local chromatin neighborhood for optimal spread of silencing, as well as the independent yet cooperative nature of the establishment of heterochromatin by the non-coding XIST RNA.

Indexed as

Epigenesis, GeneticGene SilencingChromosomes, Human, XFemaleGene Expression Regulation, DevelopmentalGenome, HumanHeterochromatinHumansRNA, Long NoncodingX Chromosome InactivationHeterochromatinRNA, Long NoncodingXIST non-coding RNA

Identifiers

PMID26429547
PMCPMC4591629
OpenAlexW2129765658

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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.