ArticleNucleic acids research2019
H3.3K4M destabilizes enhancer H3K4 methyltransferases MLL3/MLL4 and impairs adipose tissue development.
Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 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
53 citing papers in PubMed, 155 citations in OpenAlex.
- Chromatin modifiers KMT2D, cBAF, and p300 cooperatively facilitate de novo binding of transcription factors on enhancers.Nature communications · 2026Article
- Chromatin condensates tune nuclear mechanosensing and preserve nuclear integrity to prevent cGAS activation.The EMBO journal · 2026Article
- Histone tail mutants: versatile tools for decoding chromatin, development, and disease.Trends in genetics : TIG · 2026Review
- Reduced dosage of Kmt2d modifies Tbx1 haploinsufficiency toward phenotypes of 22q11.2DS.JCI insight · 2026Article
- Multiomic screening platform uncovers the impact of histone mutations on chromatin and cell fate.bioRxiv : the preprint server for biology · 2026Article
- YTH Domain Family 2 Promotes Tubal Factor Infertility through Reducing H3K4me1 Methylation of CYLD by KMT2D.Applied biochemistry and biotechnology · 2026Article
- Reducing methylation of histone 3.3 lysine 4 in the medial ganglionic eminence and hypothalamus recapitulates neurodevelopmental disorder phenotypes.Nature communications · 2026Article
- Stapled histone H3 tails are super-substrates for lysine methyltransferase SETD7.Chemical science · 2026Article
- Canonical and Non-Canonical Functions of Histone H3K4 Methylation Modifiers in Cancer.Cancer science · 2025Review
- Article
- Article
- Histone lysine methyltransferases MLL3 and MLL4 direct gene expression to produce platelets efficiently.Nature communications · 2025Article
- KMT2D coordinates antiviral CD4Cell reports · 2025Article
- Division of labor among H3K4 methyltransferases defines distinct facets of homeostatic plasticity.Cell reports · 2025Article
- Single amino acid mutations in histone H3.3 illuminate the functional significance of H3K4 methylation in plants.Nature communications · 2025Article
- Loss of Kmt2c or Kmt2d primes urothelium for tumorigenesis and redistributes KMT2A-menin to bivalent promoters.Nature genetics · 2025Article
- KMT2D-mediated H3K4me1 recruits YBX1 to facilitate triple-negative breast cancer progression through epigenetic activation of c-Myc.Clinical and translational medicine · 2024Article
- Macular dystrophy in Kabuki syndrome due to de novo KMT2D variants: refining the phenotype with multimodal imaging and follow-up over 10 years: insight into pathophysiology.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2024Article
- Unraveling the relationship between histone methylation and nonalcoholic fatty liver disease.World journal of hepatology · 2024Review
- KMT2 Family of H3K4 Methyltransferases: Enzymatic Activity-dependent and -independent Functions.Journal of molecular biology · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Histone 3 lysine 4 (H3K4) methyltransferases MLL3 and MLL4 (MLL3/4) are required for enhancer activation during cell differentiation, though the mechanism is incompletely understood. We have attempted to address this issue by generating two mouse lines: one expressing H3.3K4M, a lysine-4-to-methionine (K4M) mutation of histone H3.3 that inhibits H3K4 methylation, and the other carrying conditional double knockout of MLL3/4 enzymatic SET domain. Expression of H3.3K4M in lineage-specific precursor cells depletes H3K4 methylation and impairs adipose tissue and muscle development. Mechanistically, H3.3K4M prevents enhancer activation in adipogenesis by destabilizing MLL3/4 proteins but not other Set1-like H3K4 methyltransferases MLL1, MLL2, SET1A and SET1B. Notably, deletion of the enzymatic SET domain in lineage-specific precursor cells mimics H3.3K4M expression, destabilizes MLL3/4 proteins, and prevents adipose tissue and muscle development. Interestingly, destabilization of MLL3/4 by H3.3K4M in adipocytes does not affect adipose tissue maintenance and thermogenic function. Together, our findings indicate that expression of H3.3K4M, or deletion of the enzymatic SET domain, destabilizes enhancer H3K4 methyltransferases MLL3/4 and impairs adipose tissue and muscle development.
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.