Evidence map›Paper›PMID 39214979›Full record

ArticleNature communications2024

Histone H3.3 lysine 9 and 27 control repressive chromatin at cryptic enhancers and bivalent promoters.

Matteo Trovato, Daria Bunina, Umut Yildiz, Nadine Fernandez-Novel Marx, Michael Uckelmann, Vita Levina, Yekaterina Perez, Ana Janeva, Benjamin A Garcia, Chen Davidovich and 2 more

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing 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

13 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. Epigenome editing based treatment: Progresses and challenges.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. 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

12 authors.

Matteo TrovatoEuropean Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, Germany.ORCID 0000-0003-0406-387X
Daria BuninaEuropean Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, Germany.
Umut YildizEuropean Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, Germany.ORCID 0000-0002-7175-362X
Nadine Fernandez-Novel MarxEuropean Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, Germany.
Michael UckelmannDepartment of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Faculty of Medicine, Nursing and Health Sciences, Monash University, and EMBL-Australia, Clayton, VIC, Australia.
Vita LevinaDepartment of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Faculty of Medicine, Nursing and Health Sciences, Monash University, and EMBL-Australia, Clayton, VIC, Australia.
Yekaterina PerezDepartment of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, USA.ORCID 0000-0002-6674-4833
Ana JanevaEuropean Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, Germany.
Benjamin A GarciaDepartment of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, USA.ORCID 0000-0003-3596-4750
Chen DavidovichDepartment of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Faculty of Medicine, Nursing and Health Sciences, Monash University, and EMBL-Australia, Clayton, VIC, Australia.ORCID 0000-0002-1085-6094
Judith B ZauggEuropean Molecular Biology Laboratory (EMBL), Structural and Computational Biology Unit, Heidelberg, Germany.ORCID 0000-0001-8324-4040
Kyung-Min NohEuropean Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, Germany. kyung.min.noh@embl.de.ORCID 0000-0002-0708-787X

Funding

Shared Resources Core 2: Quantitative Proteomics CoreP01CA196539 · NCI · ROCKEFELLER UNIVERSITY · PI YOUNG, MICHAEL WARREN · 2015 to 2024
$17.6M
Viral modulation of epitranscriptomic mechanismsR01AI118891 · NIAID · WASHINGTON UNIVERSITY · PI GARCIA, BENJAMIN A, WEITZMAN, MATTHEW D. · 2015 to 2025
$5.4M
Quantitative mass spectrometry for comprehending epigenetic mechanisms in a new underlying neurological developmental disorderR01HD106051 · NICHD · WASHINGTON UNIVERSITY · PI Benjamin A Garcia · 2022 to 2026
$2.6M
Deutsche Forschungsgemeinschaft (German Research Foundation) SPP1738European Molecular Biology Laboratory (EMBL Heidelberg) MeH3NCI NIH HHS P01 CA196539NIAID NIH HHS R01 AI118891NICHD NIH HHS R01 HD106051
6 · The paper itself

Abstract

Histone modifications are associated with distinct transcriptional states, but it is unclear whether they instruct gene expression. To investigate this, we mutate histone H3.3 K9 and K27 residues in mouse embryonic stem cells (mESCs). Here, we find that H3.3K9 is essential for controlling specific distal intergenic regions and for proper H3K27me3 deposition at promoters. The H3.3K9A mutation resulted in decreased H3K9me3 at regions encompassing endogenous retroviruses and induced a gain of H3K27ac and nascent transcription. These changes in the chromatin environment unleash cryptic enhancers, resulting in the activation of distinctive transcriptional programs and culminating in protein expression normally restricted to specialized immune cell types. The H3.3K27A mutant disrupts the deposition and spreading of the repressive H3K27me3 mark, particularly impacting bivalent genes with higher basal levels of H3.3 at promoters. Therefore, H3.3K9 and K27 crucially orchestrate repressive chromatin states at cis-regulatory elements and bivalent promoters, respectively, and instruct proper transcription in mESCs.

Indexed as

ChromatinEnhancer Elements, GeneticHistonesLysineMouse Embryonic Stem CellsPromoter Regions, GeneticAnimalsEndogenous RetrovirusesHistone CodeMiceMutationTranscription, GeneticChromatinHistonesLysine

Identifiers

PMID39214979
PMCPMC11364623

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.