ArticlePLoS biology2023
Histone methyltransferase activity affects metabolism in human cells independently of transcriptional regulation.
Article in PLoS biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Role of methionine metabolism in cancer: recent advances in molecular mechanisms and therapeutic implications.Experimental hematology & oncology · 2026Review
- Hypoxic regulation of chromatin and gene transcription.Communications biology · 2026Article
- UBA6 specificity for ubiquitin E2 conjugating enzymes reveals a priority mechanism of BIRC6.Nature structural & molecular biology · 2026Article
- CRISPR targeting of H3K4me3 activates gene expression and unlocks centromere-proximal crossover recombination in Arabidopsis.Nature communications · 2025Article
- TCA-cycle metabolites in the nucleus: drivers of chromatin and epigenetic control.BMC biology · 2025Review
- Histone modifications in cervical cancer: Epigenetic mechanisms, functions and clinical implications (Review).Oncology reports · 2025Review
- The catalytic efficiency of METTL16 affects cellular processes by governing the intracellular S-adenosylmethionine setpoint.Cell reports · 2025Article
- Coordinated histone methylation loss and MYC activation promote translational capacity under amino acid restriction.Cancer & metabolism · 2025Article
- Mechanisms and rationales of SAM homeostasis.Trends in biochemical sciences · 2025Review
- Predicting substrates for orphan solute carrier proteins using multi-omics datasets.BMC genomics · 2025Article
- Macrophages: emerging targets for ulcerative colitis.Frontiers in immunology · 2025Review
- Fantastic proteins and where to find them - histones, in the nucleus and beyond.Journal of cell science · 2024Review
- The SWI/SNF chromatin remodeling complex: a critical regulator of metabolism.Biochemical Society transactions · 2024Review
- Chromatin modifiers in human disease: from functional roles to regulatory mechanisms.Molecular biomedicine · 2024Review
- Hyperacetylated histone H4 is a source of carbon contributing to lipid synthesis.The EMBO journal · 2024Article
- Regulatory RNAs: role as scaffolds assembling protein complexes and their epigenetic deregulation.Exploration of targeted anti-tumor therapy · 2024Review
- Mitochondrial electron transport chain in macrophage reprogramming: Potential role in antibacterial immune response.Current research in immunology · 2024Review
- Metabolic sinkholes: Histones as methyl repositories.PLoS biology · 2023Article
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Authors and funding
2 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The N-terminal tails of eukaryotic histones are frequently posttranslationally modified. The role of these modifications in transcriptional regulation is well-documented. However, the extent to which the enzymatic processes of histone posttranslational modification might affect metabolic regulation is less clear. Here, we investigated how histone methylation might affect metabolism using metabolomics, proteomics, and RNA-seq data from cancer cell lines, primary tumour samples and healthy tissue samples. In cancer, the expression of histone methyltransferases (HMTs) was inversely correlated to the activity of NNMT, an enzyme previously characterised as a methyl sink that disposes of excess methyl groups carried by the universal methyl donor S-adenosyl methionine (SAM or AdoMet). In healthy tissues, histone methylation was inversely correlated to the levels of an alternative methyl sink, PEMT. These associations affected the levels of multiple histone marks on chromatin genome-wide but had no detectable impact on transcriptional regulation. We show that HMTs with a variety of different associations to transcription are co-regulated by the Retinoblastoma (Rb) tumour suppressor in human cells. Rb-mutant cancers show increased total HMT activity and down-regulation of NNMT. Together, our results suggest that the total activity of HMTs affects SAM metabolism, independent of transcriptional regulation.
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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.