Evidence map›Paper›PMID 34813726›Full record

ArticleCell2021

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

Yolanda Markaki, Johnny Gan Chong, Yuying Wang, Elsie C Jacobson, Christy Luong, Shawn Y X Tan, Joanna W Jachowicz, Mackenzie Strehle, Davide Maestrini, Abhik K Banerjee and 8 more

Erratum issuedOpen access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 88 papers.

0numbers the graph read from it
0cells of the map it votes in
88citing papers in PubMed
9.8field-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

88 citing papers in PubMed, 131 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
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  6. Article
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  8. Direct roles of long non-coding RNAs in transcription activation.Nature structural & molecular biology · 2026
    Review
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  15. Article
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  20. Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 5 institutions in 2 countries.

Yolanda MarkakiDepartment of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: gmarkaki@mednet.ucla.edu.
Johnny Gan ChongDepartment of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Yuying WangDepartment of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Elsie C JacobsonDepartment of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Christy LuongDepartment of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Shawn Y X TanDepartment of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Joanna W JachowiczDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Mackenzie StrehleDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Davide MaestriniDepartment of Computational Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Abhik K BanerjeeDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Bhaven A MistryDepartment of Computational Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Claremont McKenna College, Claremont, CA 91711, USA.
Iris DrorDepartment of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Francois DossinEuropean Molecular Biology Laboratory, Director's Unit, Heidelberg 69117, Germany.
Johannes SchönebergDepartments of Pharmacology & Chemistry and Biochemistry, University of California San Diego, San Diego, CA 92093, USA.
Edith HeardEuropean Molecular Biology Laboratory, Director's Unit, Heidelberg 69117, Germany.
Mitchell GuttmanDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Tom ChouDepartment of Computational Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: tomchou@ucla.edu.
Kathrin PlathDepartment of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: kplath@mednet.ucla.edu.
University of California, Los Angeles · USCalifornia Institute of Technology · USEuropean Molecular Biology Laboratory · DEClaremont McKenna College · USUniversity of San Diego · US

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
Elucidating an Xist-dependent program of sexually dimorphic alternative splicing in the mammalian brainR01MH109166 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BLACK, DOUGLAS L, PLATH, KATHRIN · 2016 to 2020
$3.3M
Mechanism of chromatin remodeling and gene silencing by the lncRNAs Xist and TsixR01GM115233 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PLATH, KATHRIN · 2015 to 2018
$1.6M
Tracking clonal dynamics during hematopoiesis: mechanistic insight via modeling and data analysisR01HL146552 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CHOU, TOM · 2019 to 2022
$907k
Defining the role of the E3-ligase APC/C and ubiquitination in X-inactivationR21HD094172 · NICHD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DREIER, LARS, PLATH, KATHRIN · 2018 to 2019
$429k
Long Non-Coding RNA-mediated Differential Regulation of Notch Pathway Targets in Early T-cell DevelopmentF30HL136080 · NHLBI · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI BANERJEE, ABHIK · 2017 to 2021
$241k
Establishing an imaging methodology to study developmentally-regulated chromatin changes during X-chromosome InactivationR03HD095086 · NICHD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MARKAKI, GIOLANTA · 2018 to 2019
$156k
Howard Hughes Medical InstituteNCI NIH HHS P30 CA016042NHLBI NIH HHS F30 HL136080NHLBI NIH HHS R01 HL146552NICHD NIH HHS R03 HD095086NICHD NIH HHS R21 HD094172NIGMS NIH HHS R01 GM115233NIMH NIH HHS R01 MH109166
6 · The paper itself

Abstract

The lncRNA Xist forms ∼50 diffraction-limited foci to transcriptionally silence one X chromosome. How this small number of RNA foci and interacting proteins regulate a much larger number of X-linked genes is unknown. We show that Xist foci are locally confined, contain ∼2 RNA molecules, and nucleate supramolecular complexes (SMACs) that include many copies of the critical silencing protein SPEN. Aggregation and exchange of SMAC proteins generate local protein gradients that regulate broad, proximal chromatin regions. Partitioning of numerous SPEN molecules into SMACs is mediated by their intrinsically disordered regions and essential for transcriptional repression. Polycomb deposition via SMACs induces chromatin compaction and the increase in SMACs density around genes, which propagates silencing across the X chromosome. Our findings introduce a mechanism for functional nuclear compartmentalization whereby crowding of transcriptional and architectural regulators enables the silencing of many target genes by few RNA molecules.

Indexed as

AnimalsApoptosis Regulatory ProteinsCell LineEmbryonic Stem CellsFibroblastsGene SilencingHumansMiceMitochondrial ProteinsProtein BindingRNA, Long NoncodingX ChromosomeX Chromosome InactivationApoptosis Regulatory ProteinsDIABLO protein, humanMitochondrial ProteinsRNA, Long NoncodingXIST non-coding RNAbiomolecular condensateschromatin organizationheterochromatinmacromolecular dynamicsquantitative imagingRNA-binding proteinssuper-resolution microscopysupramolecular complexesX chromosome inactivationXist RNA

Identifiers

PMID34813726
PMCPMC8671326
OpenAlexW3208379306

What OpenQuestion holds

Textmetadata
LicenceTDM
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.