Evidence map›Paper›PMID 40913772›Full record

ArticleCell reports2025

Paraspeckle protein NONO regulates active chromatin by allosterically stimulating NSD1.

Chen-I Hsu, Shenglin Mei, Justin Demmerle, Anil Prakash, Sarah Ruttenberg, Mahnue Sahn, Jia-Ray Yu

Abstract read
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. 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

7 authors.

Chen-I HsuVirginia Tech Fralin Biomedical Research Institute Cancer Research Center DC, Children's National Research & Innovation Campus, Washington, DC, USA; Graduate Program in Biomedical and Veterinary Sciences (BMVS), Virginia Tech, Blacksburg, VA, USA.
Shenglin MeiVirginia Tech Fralin Biomedical Research Institute Cancer Research Center DC, Children's National Research & Innovation Campus, Washington, DC, USA; Department of Biomedical Sciences and Pathobiology (DBSP), Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA; Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC, USA.
Justin DemmerleVirginia Tech Fralin Biomedical Research Institute Cancer Research Center DC, Children's National Research & Innovation Campus, Washington, DC, USA.
Anil PrakashVirginia Tech Fralin Biomedical Research Institute Cancer Research Center DC, Children's National Research & Innovation Campus, Washington, DC, USA.
Sarah RuttenbergVirginia Tech Fralin Biomedical Research Institute Cancer Research Center DC, Children's National Research & Innovation Campus, Washington, DC, USA.
Mahnue SahnVirginia Tech Fralin Biomedical Research Institute Cancer Research Center DC, Children's National Research & Innovation Campus, Washington, DC, USA.
Jia-Ray YuVirginia Tech Fralin Biomedical Research Institute Cancer Research Center DC, Children's National Research & Innovation Campus, Washington, DC, USA; Department of Biomedical Sciences and Pathobiology (DBSP), Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA; Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC, USA. Electronic address: jiarayyu@gmail.com.

Funding

Regulation of canonical and non-canonical substrates of histone lysine methyltransferasesR35GM160046 · NIGMS · VIRGINIA POLYTECHNIC INST AND ST UNIV · PI Jia-Ray Yu · 2025 to 2026
$870k
NIGMS NIH HHS R35 GM160046
6 · The paper itself

Abstract

Nuclear receptor binding set domain protein 1 (NSD1) is a key histone methyltransferase that catalyzes di-methylation of lysine 36 of histone H3 (H3K36me2), essential for active chromatin domains. While the loss of NSD1 activity halts embryonic development and its aberrant gain drives oncogenesis in leukemia and glioma, the regulatory mechanisms remain poorly understood. Here, we uncover that NSD1 requires allosteric activation through the aromatic pocket of its Pro-Trp-Trp-Pro 2 (PWWP2) domain. Surprisingly, NSD1-PWWP2 binds to the non-canonical target, nuclear paraspeckle protein non-POU-domain-containing octamer binding protein (NONO), and this protein-protein interaction allosterically stimulates NSD1. Mouse embryonic stem cells engineered with mutations in the aromatic pocket of NSD1-PWWP2 cannot differentiate into neural progenitor cells, and genetic depletion of NONO partially phenocopies this defect, potentially explaining the neurodevelopmental disorder phenotypes in NSD1- and NONO-deficient diseases. Our work uncovers a mechanism driving active chromatin domain formation, an implication in the interplay between nuclear paraspeckles and active chromatin, and a vulnerability of NSD1 for therapeutic interventions.

Indexed as

ChromatinDNA-Binding ProteinsHistone-Lysine N-MethyltransferaseNuclear ProteinsAllosteric RegulationAnimalsHEK293 CellsHumansMiceMouse Embryonic Stem CellsProtein BindingChromatinDNA-Binding ProteinsHistone-Lysine N-MethyltransferaseNSD1 protein, humanNsd1 protein, mouseNuclear Proteinsactive chromatinCP: Molecular biologyCP: NeuroscienceepigeneticsMRXS34 syndromeneural differentiationneurodevelopmental disordersnuclear paraspecklesSotos syndromestem cells

Identifiers

PMID40913772
PMCPMC12539602

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.