{"id":"0109dbe5-af0d-562a-a23e-5d4f5d8c2244","stable_key":"97957230-601f-5dec-8524-0812be8fadbf:l-threonine-mouse-threonine-methylation","predicate":"when_depleted_reduces","statement":"Threonine withdrawal reduced SAM accumulation and H3K4 trimethylation in mouse embryonic stem cells, with slower growth and increased differentiation.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"fa055dd1-9b14-5657-bbd2-3131aff1c716","mechanism_event_label":"A nutrient supply change altered a specific epigenetic mark in this cell model.","subject":{"id":"fcef4dc2-a7b6-5812-bc33-c8af3d83f4d0","slug":"l-threonine","display_name":"L-Threonine","entity_type_key":"small_molecule"},"object":{"id":"0761a2f7-7956-5109-a4c2-0b4c8de17773","slug":"mouse-esc-sam-h3k4me3","display_name":"Mouse embryonic stem-cell SAM and H3K4 trimethylation","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"fa055dd1-9b14-5657-bbd2-3131aff1c716","stable_key":"97957230-601f-5dec-8524-0812be8fadbf:l-threonine-mouse-threonine-methylation-event","event_type":"observed_relationship","label":"A nutrient supply change altered a specific epigenetic mark in this cell model.","description":"Threonine withdrawal reduced SAM accumulation and H3K4 trimethylation in mouse embryonic stem cells, with slower growth and increased differentiation.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"fcef4dc2-a7b6-5812-bc33-c8af3d83f4d0","slug":"l-threonine","display_name":"L-Threonine","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"0761a2f7-7956-5109-a4c2-0b4c8de17773","slug":"mouse-esc-sam-h3k4me3","display_name":"Mouse embryonic stem-cell SAM and H3K4 trimethylation","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":"2b507258-430c-51fe-9fd2-e510c2c197a9","slug":"glycine","display_name":"Glycine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"b7ed6e4c-e560-5cee-b68f-895f21862e6f","slug":"acetyl-coa","display_name":"Acetyl-CoA","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":4,"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 abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Mouse stem-cell isotope tracing and culture-medium withdrawal.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Do not generalize to all methylation marks, adult human tissues or a threonine treatment for methylation problems.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Threonine collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"l-threonine","display_name":"L-Threonine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"A nutrient supply change altered a specific epigenetic mark in this cell model.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Influence of threonine metabolism on S-adenosylmethionine and histone methylation. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23118012/ · DOI 10.1126/science.1226603","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":"3ba879c8-7a6b-5d21-96c3-06ccd7196fd4","evidence_kind":"source_excerpt","locator":"Lines 330-336","start_line":330,"end_line":336,"excerpt":"## l-threonine-mouse-threonine-methylation\nA nutrient supply change altered a specific epigenetic mark in this cell model.\nThreonine withdrawal reduced SAM accumulation and H3K4 trimethylation in mouse embryonic stem cells, with slower growth and increased differentiation.\nModel: Mouse stem-cell isotope tracing and culture-medium withdrawal.\nLimitations: Do not generalize to all methylation marks, adult human tissues or a threonine treatment for methylation problems.\nEvidence access: Primary abstract\nInfluence of threonine metabolism on S-adenosylmethionine and histone methylation. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23118012/ · DOI 10.1126/science.1226603","model_system":"Mouse stem-cell isotope tracing and culture-medium withdrawal.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; 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