ArticleProceedings of the National Academy of Sciences of the United States of America2022
TGM2-mediated histone transglutamination is dictated by steric accessibility.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 33 citations in OpenAlex.
- Chemical Proteomic Profiling of the Histaminylation Proteome in Cancer Cells Unveils Uncharted Epigenetic Marks on Core Histones.Journal of the American Chemical Society · 2026Article
- Traceless protein semisynthesis in cells using the promiscuous ultra-fast split intein NrdJ-1.Chemical science · 2026Article
- Histone Modifications in Psychiatry: From Canonical Marks to Neurotransmitter-Mediated Epigenetic Signatures.Alpha psychiatry · 2026Review
- Beyond neurotransmission: the roles of serotonylation in physiological and pathological processes.Cellular & molecular biology letters · 2026Review
- Review
- Quinone reductase 2bioRxiv : the preprint server for biology · 2026Article
- Traceless protein semi-synthesis in cells using the promiscuous ultra-fast split intein NrdJ-1.bioRxiv : the preprint server for biology · 2026Article
- Monoaminylation in Human Health and Disease: State of the Field, Challenges, and Emerging Directions.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Chromatin Accessibility in Cancer: Biological Functions, Mechanisms, Therapeutic Potential, and Future Directions.MedComm · 2026Review
- Interaction of serotonin transporter and TGFB1 facilitates histone serotonylation-mediated synaptic plasticity following environmental enrichment in stressed mouse Mus booduga.Epigenetics & chromatin · 2026Article
- Reimagining biogenic amine signaling in the brain and beyond.Trends in neurosciences · 2026Review
- Transglutaminase-2 Promotes Microglial Synaptic Phagocytosis and Ameliorates Epileptic Seizures by Inhibiting ABCA1 Ubiquitination.CNS neuroscience & therapeutics · 2025Article
- Mechanical control of histone serotonylation initiates neural crest migrationbioRxiv : the preprint server for biology · 2025Article
- Molecular determinants for recognition of serotonylated chromatin.Nucleic acids research · 2025Article
- Article
- Elucidating neuroepigenetic mechanisms to inform targeted therapeutics for brain disorders.iScience · 2025Review
- Identification of transglutaminase 2 mediated polyaminated proteins in a hepatocellular cancer cell line.Computational and structural biotechnology journal · 2025Article
- Article
- Chromatin accessibility: biological functions, molecular mechanisms and therapeutic application.Signal transduction and targeted therapy · 2024Review
- Whole exome sequencing analyses identified novel genes for Alzheimer's disease and related dementia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Recent studies have identified serotonylation of glutamine-5 on histone H3 (H3Q5ser) as a novel posttranslational modification (PTM) associated with active transcription. While H3Q5ser is known to be installed by tissue transglutaminase 2 (TGM2), the substrate characteristics affecting deposition of the mark, at the level of both chromatin and individual nucleosomes, remain poorly understood. Here, we show that histone serotonylation is excluded from constitutive heterochromatic regions in mammalian cells. Biochemical studies reveal that the formation of higher-order chromatin structures associated with heterochromatin impose a steric barrier that is refractory to TGM2-mediated histone monoaminylation. A series of structure-activity relationship studies, including the use of DNA-barcoded nucleosome libraries, shows that steric hindrance also steers TGM2 activity at the nucleosome level, restricting monoaminylation to accessible sites within histone tails. Collectively, our data indicate that the activity of TGM2 on chromatin is dictated by substrate accessibility rather than by primary sequence determinants or by the existence of preexisting PTMs, as is the case for many other histone-modifying enzymes.
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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.