Histone H3 lysine 4 trimethylation: molecular mechanisms & dependencies

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

Human evidence only

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

Where it participates (unsigned role)

Network-level integration of transcriptomics and metabolomics data identifies glycolysis, glutaminolysis and the cholesterol synthesis pathway as indispensable for the induction of trained immunity by beta-glucan in monocytes, accumulation of fumarate due to glutamine replenishment of the TCA cycle integrates immune and metabolic circuits to induce monocyte epigenetic reprogramming by inhibiting KDM5 histone demethylases, fumarate itself induced an epigenetic program similar to beta-glucan-induced trained immunity, and inhibition of glutaminolysis and cholesterol synthesis in mice reduced the induction of trained immunity by beta-glucan.
Fumarate → KDM5 histone demethylases source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glucan-research/27866838.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c67ca385f9dd5e9e97432aa9141a594b7121acca8eea6eba3d0738fed75deba8", "start_char": 0, "end_char": 1031, "text_sha256": "c67ca385f9dd5e9e97432aa9141a594b7121acca8eea6eba3d0738fed75deba8"}
experimental_model
Network integration of transcriptomics and metabolomics with pathway inhibition in monocytes and in mice
exposure
Beta-glucan training with inhibition of glutaminolysis and cholesterol synthesis, and fumarate given alone
limitations
Fumarate reproducing the epigenetic programme on its own is the strongest part. The link runs through inhibition of a demethylase, which is not the same modification as an acetylation mark.
nutrient_topic
Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair. · Beta-glucan
organism
Human cells and mouse
plain_language
A metabolite piles up and jams the enzyme that would strip the marks off, so the marks stay.
primary_references
[bg-p27866838] Glutaminolysis and Fumarate Accumulation Integrate Immunometabolic and Epigenetic Programs in Trained Immunity. (2016). https://pubmed.ncbi.nlm.nih.gov/27866838/ DOI: 10.1016/j.cmet.2016.10.008
tissue_or_cell_type
Monocyte
Beta-glucan: a structural family rather than an agent, what decides whether a bound glucan actually signals, the complement route that a cereal and a yeast preparation share, and the unequal human evidence behind each (2026-09-22) · lines 450–461
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Network integration of transcriptomics and metabolomics with pathway inhibition in monocytes and in mice · source_derived_draft · unverified_draft
### bg-fumarate-blocks-a-demethylase Network-level integration of transcriptomics and metabolomics data identifies glycolysis, glutaminolysis and the cholesterol synthesis pathway as indispensable for the induction of trained immunity by beta-glucan in monocytes, accumulation of fumarate due to glutamine replenishment of the TCA cycle integrates immune and metabolic circuits to induce monocyte epigenetic reprogramming by inhibiting KDM5 histone demethylases, fumarate itself induced an epigenetic program similar to beta-glucan-induced trained immunity, and inhibition of glutaminolysis and cholesterol synthesis in mice reduced the induction of trained immunity by beta-glucan. Condition category: normal nutrient_topic: Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair. plain_language: A metabolite piles up and jams the enzyme that would strip the marks off, so the marks stay. organism: Human cells and mouse tissue_or_cell_type: Monocyte experimental_model: Network integration of transcriptomics and metabolomics with pathway inhibition in monocytes and in mice limitations: Fumarate reproducing the epigenetic programme on its own is the strongest part. The link runs through inhibition of a demethylase, which is not the same modification as an acetylation mark. exposure: Beta-glucan training with inhibition of glutaminolysis and cholesterol synthesis, and fumarate given alone evidence_span: {"source_cache": "artifacts/glucan-research/27866838.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c67ca385f9dd5e9e97432aa9141a594b7121acca8eea6eba3d0738fed75deba8", "start_char": 0, "end_char": 1031, "text_sha256": "c67ca385f9dd5e9e97432aa9141a594b7121acca8eea6eba3d0738fed75deba8"} [bg-p27866838] Glutaminolysis and Fumarate Accumulation Integrate Immunometabolic and Epigenetic Programs in Trained Immunity. (2016). https://pubmed.ncbi.nlm.nih.gov/27866838/ DOI: 10.1016/j.cmet.2016.10.008
Complete structured claim and evidence
Mice lacking functional T and B lymphocytes are protected against reinfection with Candida albicans in a monocyte-dependent manner, C. albicans and fungal cell wall beta-glucans induced functional reprogramming of monocytes leading to enhanced cytokine production in vivo and in vitro, the training required the beta-glucan receptor dectin-1 and the noncanonical Raf-1 pathway, and monocyte training by beta-glucans was associated with stable changes in histone trimethylation at H3K4 which suggests the involvement of epigenetic mechanisms.
Beta-glucan → Trained immunity, an altered response to a later challenge after the first has ended source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glucan-research/22901542.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "75bc4bedb7017f3d94d8f7441862392ddca229ed16f93eb528d3f9df3da66408", "start_char": 0, "end_char": 1067, "text_sha256": "75bc4bedb7017f3d94d8f7441862392ddca229ed16f93eb528d3f9df3da66408"}
experimental_model
Reinfection protection in mice lacking functional T and B lymphocytes, with monocyte reprogramming in vitro and in vivo
exposure
Candida albicans and fungal cell wall beta-glucans as the training stimulus, with the first exposure resolved before rechallenge
limitations
The Raf-1 dependence belongs to this training protocol. It does not establish that every beta-glucan training protocol is independent of the canonical Syk route.
nutrient_topic
Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair. · Beta-glucan
organism
Mouse
plain_language
Animals with no adaptive immune system at all were still protected the second time, because their monocytes had been rewired.
primary_references
[bg-p22901542] Candida albicans infection affords protection against reinfection via functional reprogramming of monocytes. (2012). https://pubmed.ncbi.nlm.nih.gov/22901542/ DOI: 10.1016/j.chom.2012.06.006
tissue_or_cell_type
Monocyte
Beta-glucan: a structural family rather than an agent, what decides whether a bound glucan actually signals, the complement route that a cereal and a yeast preparation share, and the unequal human evidence behind each (2026-09-22) · lines 424–435
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Reinfection protection in mice lacking functional T and B lymphocytes, with monocyte reprogramming in vitro and in vivo · source_derived_draft · unverified_draft
### bg-training-runs-through-raf1 Mice lacking functional T and B lymphocytes are protected against reinfection with Candida albicans in a monocyte-dependent manner, C. albicans and fungal cell wall beta-glucans induced functional reprogramming of monocytes leading to enhanced cytokine production in vivo and in vitro, the training required the beta-glucan receptor dectin-1 and the noncanonical Raf-1 pathway, and monocyte training by beta-glucans was associated with stable changes in histone trimethylation at H3K4 which suggests the involvement of epigenetic mechanisms. Condition category: normal nutrient_topic: Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair. plain_language: Animals with no adaptive immune system at all were still protected the second time, because their monocytes had been rewired. organism: Mouse tissue_or_cell_type: Monocyte experimental_model: Reinfection protection in mice lacking functional T and B lymphocytes, with monocyte reprogramming in vitro and in vivo limitations: The Raf-1 dependence belongs to this training protocol. It does not establish that every beta-glucan training protocol is independent of the canonical Syk route. exposure: Candida albicans and fungal cell wall beta-glucans as the training stimulus, with the first exposure resolved before rechallenge evidence_span: {"source_cache": "artifacts/glucan-research/22901542.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "75bc4bedb7017f3d94d8f7441862392ddca229ed16f93eb528d3f9df3da66408", "start_char": 0, "end_char": 1067, "text_sha256": "75bc4bedb7017f3d94d8f7441862392ddca229ed16f93eb528d3f9df3da66408"} [bg-p22901542] Candida albicans infection affords protection against reinfection via functional reprogramming of monocytes. (2012). https://pubmed.ncbi.nlm.nih.gov/22901542/ DOI: 10.1016/j.chom.2012.06.006
Complete structured claim and evidence

The events it takes part in

A mechanism often involves more than two components. These are the full events, with every participant and its role.

Situations it appears in

Low-supply and faulty-machinery situations recorded in the chapters where this component plays a part.

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

Open hypotheses

Proposed ideas that involve this component. They are labeled as hypotheses and do not change any recorded statement.

This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

Histone H3 lysine 4 trimethylation