{"id":"742ba896-e1d6-5964-a5d9-2de64efccb84","stable_key":"41a89233-da9a-5b7b-9c18-e19bbadcfe2d:methionine-dot1l-gate","predicate":"enables_tested","statement":"T-cell Dot1l deletion removed H3K79me2 and prevented methionine supplementation from rescuing tumor-medium-induced apoptosis and impaired cytokine production.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"75073d43-aebe-5b7b-9ebc-c8101275d4f8","mechanism_event_label":"Supplying the nutrient failed when the downstream methyltransferase was absent.","subject":{"id":"7edfa059-9bb4-53e5-95e9-149154e6adef","slug":"mouse-dot1l","display_name":"Mouse histone H3K79 methyltransferase / Dot1l","entity_type_key":"protein"},"object":{"id":"3762b1d6-b4e8-5852-8172-3eb918725235","slug":"mouse-methionine-tcell-rescue","display_name":"Methionine rescue of mouse T-cell survival and function","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"75073d43-aebe-5b7b-9ebc-c8101275d4f8","stable_key":"41a89233-da9a-5b7b-9c18-e19bbadcfe2d:methionine-dot1l-gate-event","event_type":"observed_relationship","label":"Supplying the nutrient failed when the downstream methyltransferase was absent.","description":"T-cell Dot1l deletion removed H3K79me2 and prevented methionine supplementation from rescuing tumor-medium-induced apoptosis and impaired cytokine production.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"7edfa059-9bb4-53e5-95e9-149154e6adef","slug":"mouse-dot1l","display_name":"Mouse histone H3K79 methyltransferase / Dot1l","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"3762b1d6-b4e8-5852-8172-3eb918725235","slug":"mouse-methionine-tcell-rescue","display_name":"Methionine rescue of mouse T-cell survival and function","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"9d39f561-740b-5f67-bba7-8a72ef612a99","slug":"methionine","display_name":"L-Methionine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"825f2da2-01bc-5874-a3c6-64f5ac867db5","slug":"s-adenosylmethionine","display_name":"S-Adenosyl-L-methionine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_access","value_text":"Primary full text","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Conditional mouse T-cell Dot1l knockout and culture add-back experiments.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Not a claim that dietary methionine deficiency causes DOT1L loss; gene loss and substrate shortage are distinct. Correction record: Author correction published online 12 December 2025 (2026 issue): Extended Data Fig. 1j originally duplicated the A375-supernatant flow-cytometry plot in the Sup+Ser condition; publisher replaced the representative image. This is a figure correction, not an opposing scientific finding. https://www.nature.com/articles/s41586-025-09845-8","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Methionine collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"methionine","display_name":"L-Methionine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"Supplying the nutrient failed when the downstream methyltransferase was absent.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Cancer SLC43A2 alters T cell methionine metabolism and histone methylation. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32879489/ · DOI 10.1038/s41586-020-2682-1","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"77a68edc-9bc2-5fcb-a916-1bad06c8d419","evidence_kind":"source_excerpt","locator":"Lines 348-354","start_line":348,"end_line":354,"excerpt":"## methionine-dot1l-gate\nSupplying the nutrient failed when the downstream methyltransferase was absent.\nT-cell Dot1l deletion removed H3K79me2 and prevented methionine supplementation from rescuing tumor-medium-induced apoptosis and impaired cytokine production.\nModel: Conditional mouse T-cell Dot1l knockout and culture add-back experiments.\nLimitations: Not a claim that dietary methionine deficiency causes DOT1L loss; gene loss and substrate shortage are distinct. Correction record: Author correction published online 12 December 2025 (2026 issue): Extended Data Fig. 1j originally duplicated the A375-supernatant flow-cytometry plot in the Sup+Ser condition; publisher replaced the representative image. This is a figure correction, not an opposing scientific finding. https://www.nature.com/articles/s41586-025-09845-8\nEvidence access: Primary full text\nCancer SLC43A2 alters T cell methionine metabolism and histone methylation. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32879489/ · DOI 10.1038/s41586-020-2682-1","model_system":"Conditional mouse T-cell Dot1l knockout and culture add-back experiments.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access and experimental limitations specified.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"d969b004-ccc2-5bb4-9109-8ac649137ad1","stable_key":"import-41a89233-da9a-5b7b-9c18-e19bbadcfe2d","title":"L-Methionine: transport, methylation, sulfur metabolism and cross-nutrient mechanisms (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text.","file_path":"","sha256":"f1c706ef72932eed85df234b6c3304158d503d626a63c69b02a453c162700d26","revision_id":"549035e0-3a72-550a-8a55-e8c5baa51b0d","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}