ArticleNature communications2019
H3.3K27M-induced chromatin changes drive ectopic replication through misregulation of the JNK pathway in C. elegans.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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.
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.
Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- Transgenerational inheritance of altered H3K27me3 in wild-type Caenorhabditis elegans.The EMBO journal · 2026Article
- SSUP-72/PINN-1 coordinates RNA-polymerase II 3' pausing and developmental gene expression in C. elegans.Nature communications · 2025Article
- Multi-omics approaches reveal that diffuse midline gliomas present altered DNA replication and are susceptible to replication stress therapy.Genome biology · 2024Article
- An E2 ubiquitin-conjugating enzyme links diubiquitinated H2B to H3K27M oncohistone function.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Emerging roles of cancer-associated histone mutations in genomic instabilities.Frontiers in cell and developmental biology · 2024Review
- Caenorhabditis elegans for research on cancer hallmarks.Disease models & mechanisms · 2023Article
- H3F3A K27M Mutation Promotes the Infiltrative Growth of High-Grade Glioma in Adults by Activating β-Catenin/USP1 Signaling.Cancers · 2022Article
- Article
- Inhibition of histone H3-H4 chaperone pathways rescues C. elegans sterility by H2B loss.PLoS genetics · 2022Article
- Impact of Chromatin Dynamics and DNA Repair on Genomic Stability and Treatment Resistance in Pediatric High-Grade Gliomas.Cancers · 2021Review
- Polycomb repressive complex 2 in the driver's seat of childhood and young adult brain tumours.Trends in cell biology · 2021Review
- Synthetic lethality and synergetic effect: the effective strategies for therapy of IDH-mutated cancers.Journal of experimental & clinical cancer research : CR · 2021Review
- Harnessing the power of genetics: fast forward genetics in Caenorhabditis elegans.Molecular genetics and genomics : MGG · 2021Review
- Loss of histone H3.3 results in DNA replication defects and altered origin dynamics inGenome research · 2020Article
- Histone deposition pathways determine the chromatin landscapes of H3.1 and H3.3 K27M oncohistones.eLife · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Substitution of lysine 27 with methionine in histone H3.3 is a recently discovered driver mutation of pediatric high-grade gliomas. Mutant cells show decreased levels and altered distribution of H3K27 trimethylation (H3K27me3). How these chromatin changes are established genome-wide and lead to tumorigenesis remains unclear. Here we show that H3.3K27M-mediated alterations in H3K27me3 distribution result in ectopic DNA replication and cell cycle progression of germ cells in Caenorhabditis elegans. By genetically inducing changes in the H3.3 distribution, we demonstrate that both H3.3K27M and pre-existing H3K27me3 act locally and antagonistically on Polycomb Repressive Complex 2 (PRC2) in a concentration-dependent manner. The heterochromatin changes result in extensive gene misregulation, and genetic screening identified upregulation of JNK as an underlying cause of the germcell aberrations. Moreover, JNK inhibition suppresses the replicative fate in human tumor-derived H3.3K27M cells, thus establishing C. elegans as a powerful model for the identification of potential drug targets for treatment of H3.3K27M tumors.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.