Evidence map›Paper›PMID 40402740›Full record

ArticleCell reports2025

Division of labor among H3K4 methyltransferases defines distinct facets of homeostatic plasticity.

Takao Tsukahara, Saini Kethireddy, Katherine M Bonefas, Alex Chen, Brendan L M Sutton, Kenjiro Bandow, Yali Dou, Shigeki Iwase, Michael A Sutton

Abstract read
PubMed Full text at PMC Publisher
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 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. bioRxiv : the preprint server for biology · 2026
    Article
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Takao TsukaharaMichigan Neuroscience Institute, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA; Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA; Meikai University School of Dentistry, Department of Oral Biology and Tissue Engineering, Division of Biochemistry, Sakado, Saitama 350-0283, Japan.
Saini KethireddyCollege of Literature, Science, and the Arts, University of Michigan, Ann Arbor, MI 48109, USA.
Katherine M BonefasNeuroscience Graduate Program, University of Michigan, Ann Arbor, MI 48109, USA.
Alex ChenNeuroscience Graduate Program, University of Michigan, Ann Arbor, MI 48109, USA.
Brendan L M SuttonDepartment of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
Kenjiro BandowMeikai University School of Dentistry, Department of Oral Biology and Tissue Engineering, Division of Biochemistry, Sakado, Saitama 350-0283, Japan.
Yali DouDepartment of Medicine and Department of Biochemistry and Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Shigeki IwaseMichigan Neuroscience Institute, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: siwase@umich.edu.
Michael A SuttonMichigan Neuroscience Institute, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA. Electronic address: masutton@umich.edu.

Funding

Trans-synaptic control of presynaptic neurotransmitter releaseR01NS097498 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SUTTON, MICHAEL MARK ALEXANDER · 2016 to 2025
$3.8M
A Neuron-specific Methyl-histone Regulatory ComplexR01NS116008 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Shigeki Iwase · 2020 to 2026
$3.6M
Dissecting Histone H3K4 Methylation Enzymes in NeuroplasticityR01MH133632 · NIMH · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Shigeki Iwase, Michael Mark Alexander Sutton · 2024 to 2026
$2.0M
Diurnal Experimental Models to Investigate Neural Mechanisms of Sleep Disturbance in Smith-Magenis SyndromeR21NS125449 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI IWASE, SHIGEKI, YAN, LILY · 2021 to 2021
$444k
Neuronal Activity-dependent Pomoter UsageR21MH127485 · NIMH · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI IWASE, SHIGEKI · 2022 to 2023
$418k
NIMH NIH HHS R01 MH133632NIMH NIH HHS R21 MH127485NINDS NIH HHS R01 NS097498NINDS NIH HHS R01 NS116008NINDS NIH HHS R21 NS125449
6 · The paper itself

Abstract

Heterozygous mutations in any of the six H3K4 methyltransferases (KMT2s) result in monogenic neurodevelopmental disorders, indicating non-redundant yet poorly understood roles of this enzyme family in neurodevelopment. However, the specific cellular role of KMT2 enzymes in the brain remains poorly understood, owing to the clear non-catalytic functions of each family member and the potential for functional redundancy in installing H3K4 methylation (H3K4me). Here, we identify an instructive role for H3K4me in controlling synapse function and a division of labor among the six KMT2 enzymes in regulating homeostatic synaptic scaling. Using RNAi screening, conditional genetics, small-molecule inhibitors, and transcriptional profiling, our data reveal that individual KMT2 enzymes have unique roles and operate in specific phases to control distinct facets of homeostatic scaling. Together, our results suggest that the expansion of this enzyme family in mammals is key to coupling fine-tuned gene expression changes to adaptive modifications of synaptic function.

Indexed as

Histone-Lysine N-MethyltransferaseHistonesHomeostasisNeuronal PlasticityAnimalsHumansMethylationMiceSynapsesHistone-Lysine N-MethyltransferaseHistoneschromatinCP: Neurosciencehistone methylationhomeostatic plasticityKMT2lysine methyltransferase 2neurodevelopmental disorderstranscription

Identifiers

PMID40402740
PMCPMC12289303

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.