{"id":"e08c2504-f9dd-5b10-bdf0-8a241b298a09","stable_key":"41a89233-da9a-5b7b-9c18-e19bbadcfe2d:methionine-tcell-histone-stat5","predicate":"restores_under_tested_shortage","statement":"Human T cells exposed to tumor supernatants lost H3K79 methylation; adding methionine to human colorectal tumor-infiltrating T-cell cultures improved H3K79me2 and STAT5 readouts.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"84ddf150-4600-5615-88de-bd4b964dcd1a","mechanism_event_label":"Nutrient competition reached a specific chromatin and signaling program.","subject":{"id":"9d39f561-740b-5f67-bba7-8a72ef612a99","slug":"methionine","display_name":"L-Methionine","entity_type_key":"small_molecule"},"object":{"id":"db03697f-ec82-5e2d-a83c-998abbc3cc5a","slug":"human-tcell-h3k79me2-stat5","display_name":"H3K79me2 and STAT5 expression in human T cells","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"84ddf150-4600-5615-88de-bd4b964dcd1a","stable_key":"41a89233-da9a-5b7b-9c18-e19bbadcfe2d:methionine-tcell-histone-stat5-event","event_type":"observed_relationship","label":"Nutrient competition reached a specific chromatin and signaling program.","description":"Human T cells exposed to tumor supernatants lost H3K79 methylation; adding methionine to human colorectal tumor-infiltrating T-cell cultures improved H3K79me2 and STAT5 readouts.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"9d39f561-740b-5f67-bba7-8a72ef612a99","slug":"methionine","display_name":"L-Methionine","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"db03697f-ec82-5e2d-a83c-998abbc3cc5a","slug":"human-tcell-h3k79me2-stat5","display_name":"H3K79me2 and STAT5 expression in human T cells","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"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":2,"notes":""},{"entity":{"id":"d8de1e6a-fdad-52a0-8b9d-c9ea510a0238","slug":"stat5","display_name":"STAT5","entity_type_key":"protein_family"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"nutrient_deficiency","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":"Human A375-conditioned T cells and colorectal tumor-infiltrating T cells ex vivo; Extended Data Figs. 2k and 4j-m.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"A defined histone mark is not a global DNA methylation readout; not a validated oral cancer treatment. 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":"Nutrient competition reached a specific chromatin and signaling program.","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":"nutrient_deficiency","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"46f85013-9438-5e2c-9bae-247764749886","evidence_kind":"source_excerpt","locator":"Lines 436-442","start_line":436,"end_line":442,"excerpt":"## methionine-tcell-histone-stat5\nNutrient competition reached a specific chromatin and signaling program.\nHuman T cells exposed to tumor supernatants lost H3K79 methylation; adding methionine to human colorectal tumor-infiltrating T-cell cultures improved H3K79me2 and STAT5 readouts.\nModel: Human A375-conditioned T cells and colorectal tumor-infiltrating T cells ex vivo; Extended Data Figs. 2k and 4j-m.\nLimitations: A defined histone mark is not a global DNA methylation readout; not a validated oral cancer treatment. 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":"Human A375-conditioned T cells and colorectal tumor-infiltrating T cells ex vivo; Extended Data Figs. 2k and 4j-m.","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}