Evidence map›Paper›PMID 38815580›Full record

ArticleCell2024

RNA quality control factors nucleate Clr4/SUV39H and trigger constitutive heterochromatin assembly.

Jasbeer S Khanduja, Richard I Joh, Monica M Perez, Joao A Paulo, Christina M Palmieri, Jingyu Zhang, Alex O D Gulka, Willhelm Haas, Steven P Gygi, Mo Motamedi

Abstract read
In one paragraph

Article in Cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing 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

18 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Humanization of theGenes · 2026
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Fungi as models of centromere innovation: from DNA sequence to 3-dimensional arrangement.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2025
    Review
  15. Article
  16. Article
  17. Review
  18. 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

10 authors.

Jasbeer S KhandujaMassachusetts General Hospital Krantz Family Center for Cancer Research and Department of Medicine, Harvard Medical School, Charlestown, MA 02129, USA.
Richard I JohMassachusetts General Hospital Krantz Family Center for Cancer Research and Department of Medicine, Harvard Medical School, Charlestown, MA 02129, USA.
Monica M PerezMassachusetts General Hospital Krantz Family Center for Cancer Research and Department of Medicine, Harvard Medical School, Charlestown, MA 02129, USA.
Joao A PauloDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Christina M PalmieriMassachusetts General Hospital Krantz Family Center for Cancer Research and Department of Medicine, Harvard Medical School, Charlestown, MA 02129, USA.
Jingyu ZhangMassachusetts General Hospital Krantz Family Center for Cancer Research and Department of Medicine, Harvard Medical School, Charlestown, MA 02129, USA.
Alex O D GulkaMassachusetts General Hospital Krantz Family Center for Cancer Research and Department of Medicine, Harvard Medical School, Charlestown, MA 02129, USA.
Willhelm HaasMassachusetts General Hospital Krantz Family Center for Cancer Research and Department of Medicine, Harvard Medical School, Charlestown, MA 02129, USA.
Steven P GygiDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Mo MotamediMassachusetts General Hospital Krantz Family Center for Cancer Research and Department of Medicine, Harvard Medical School, Charlestown, MA 02129, USA. Electronic address: mmotamedi@hms.harvard.edu.

Funding

New Sample Multiplexing Technologies to Identify Chemical Probes and Illuminate Ubiquitin BiologyR01GM067945 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI GYGI, STEVEN P · 2003 to 2024
$10.5M
Quiescent-induced transcriptional regulationR01GM125782 · NIGMS · MASSACHUSETTS GENERAL HOSPITAL · PI MOTAMEDI, MO · 2017 to 2020
$1.4M
NIGMS NIH HHS R01 GM067945NIGMS NIH HHS R01 GM125782
6 · The paper itself

Abstract

In eukaryotes, the Suv39 family of proteins tri-methylate lysine 9 of histone H3 (H3K9me) to form constitutive heterochromatin. However, how Suv39 proteins are nucleated at heterochromatin is not fully described. In the fission yeast, current models posit that Argonaute1-associated small RNAs (sRNAs) nucleate the sole H3K9 methyltransferase, Clr4/SUV39H, to centromeres. Here, we show that in the absence of all sRNAs and H3K9me, the Mtl1 and Red1 core (MTREC)/PAXT complex nucleates Clr4/SUV39H at a heterochromatic long noncoding RNA (lncRNA) at which the two H3K9 deacetylases, Sir2 and Clr3, also accumulate by distinct mechanisms. Iterative cycles of H3K9 deacetylation and methylation spread Clr4/SUV39H from the nucleation center in an sRNA-independent manner, generating a basal H3K9me state. This is acted upon by the RNAi machinery to augment and amplify the Clr4/H3K9me signal at centromeres to establish heterochromatin. Overall, our data reveal that lncRNAs and RNA quality control factors can nucleate heterochromatin and function as epigenetic silencers in eukaryotes.

Indexed as

Cell Cycle ProteinsHeterochromatinHistone-Lysine N-MethyltransferaseHistonesSchizosaccharomycesSchizosaccharomyces pombe ProteinsArgonaute ProteinsCentromereMethylationMethyltransferasesRNA, FungalRNA, Long NoncodingRNA, Small InterferingAgo1 protein, S pombeArgonaute ProteinsCell Cycle Proteinsclr4 protein, S pombeHeterochromatinHistone-Lysine N-MethyltransferaseHistonesMethyltransferasesRNA, FungalRNA, Long NoncodingRNA, Small InterferingSchizosaccharomyces pombe ProteinsClr3Clr4/SUV39Hde novo heterochromatin formationH3K9 deacetylation and methylationheterochromatin nucleationlong noncoding RNAsMtl1MTREC/NURSnuclear exosomeSir2

Identifiers

PMID38815580
PMCPMC11227895

What OpenQuestion holds

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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.