{"id":"87327604-c293-5cf4-b882-afdf45e1940e","stable_key":"cb568d28-484a-5c2e-9fcc-2d780358e514:c-reg-esc-promoter-demethylation","predicate":"decreases","statement":"After vitamin C derivative treatment, numerous mouse ESC promoters lost methylcytosine; imprinted regions and IAP retroelements were relatively resistant, so the effect was not indiscriminate erasure of genomic methylation.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"bc502727-8995-5dd4-a3ae-88be90212bb7","mechanism_event_label":"Vitamin C changed selected DNA methylation patterns in these cells; protected regions retained their marks.","subject":{"id":"46fcdd0b-e1cb-59f0-ba15-80f13a2c904b","slug":"ascorbate-2-phosphate","display_name":"L-Ascorbic acid 2-phosphate","entity_type_key":"small_molecule"},"object":{"id":"1845fcad-6b15-51c8-9dc0-4328d51ce35c","slug":"gene-promoter-dna-methylation","display_name":"Gene-promoter DNA methylation","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"bc502727-8995-5dd4-a3ae-88be90212bb7","stable_key":"cb568d28-484a-5c2e-9fcc-2d780358e514:c-reg-esc-promoter-demethylation-event","event_type":"biochemical_relationship","label":"Vitamin C changed selected DNA methylation patterns in these cells; protected regions retained their marks.","description":"After vitamin C derivative treatment, numerous mouse ESC promoters lost methylcytosine; imprinted regions and IAP retroelements were relatively resistant, so the effect was not indiscriminate erasure of genomic methylation.","status":"provisional","compartment":{"slug":"nucleus","display_name":"Nucleus"},"participants":[{"entity":{"id":"da1a7137-08f2-5a36-8bb6-377fbd32e327","slug":"vitamin-c","display_name":"Vitamin C","entity_type_key":"chemical_species"},"role":"nutrient context","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"be39243b-1d20-58c9-9f76-1480560334ac","slug":"tet1-mouse","display_name":"Mouse Tet1","entity_type_key":"protein"},"role":"enzyme","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"36d7160b-6534-58a6-a0df-55bcde8e740c","slug":"tet2-mouse","display_name":"Mouse Tet2","entity_type_key":"protein"},"role":"enzyme","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"a28c2ffa-8f0b-530a-91e0-770c661a3583","slug":"genomic-dna-methylation","display_name":"Genomic DNA methylation","entity_type_key":"cellular_process"},"role":"related process","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"46fcdd0b-e1cb-59f0-ba15-80f13a2c904b","slug":"ascorbate-2-phosphate","display_name":"L-Ascorbic acid 2-phosphate","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"1845fcad-6b15-51c8-9dc0-4328d51ce35c","slug":"gene-promoter-dna-methylation","display_name":"Gene-promoter DNA methylation","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"false","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_location","value_text":"Figure 2; resistant-region analysis","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Mouse Oct4-GiP ESCs in feeder-free 2i/LIF medium; DNA dot blot and hydroxymethyl-DNA immunoprecipitation; mC-DIP sequencing/qPCR and bisulfite validation","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"100 µg/mL L-ascorbic acid 2-phosphate (A8960), medium replaced daily; 12-h and 72-h sampling.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Locus-selective cell-culture result; promoter demethylation did not automatically activate every affected gene.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Vitamin C research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"vitamin-c","display_name":"Vitamin C","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Mus musculus","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Vitamin C changed selected DNA methylation patterns in these cells; protected regions retained their marks.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[c-reg-blaschke] Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells. (2013). https://pubmed.ncbi.nlm.nih.gov/23812591/ DOI: 10.1038/nature12362","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Embryonic stem cells","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"b1f6c601-f989-5f06-a363-9f4548334c7a","evidence_kind":"source_excerpt","locator":"Lines 991-1003","start_line":991,"end_line":1003,"excerpt":"### c-reg-esc-promoter-demethylation\nAfter vitamin C derivative treatment, numerous mouse ESC promoters lost methylcytosine; imprinted regions and IAP retroelements were relatively resistant, so the effect was not indiscriminate erasure of genomic methylation.\nCondition category: normal\nnutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Vitamin C changed selected DNA methylation patterns in these cells; protected regions retained their marks.\norganism: Mus musculus\ntissue_or_cell_type: Embryonic stem cells\nexperimental_model: Mouse Oct4-GiP ESCs in feeder-free 2i/LIF medium; DNA dot blot and hydroxymethyl-DNA immunoprecipitation; mC-DIP sequencing/qPCR and bisulfite validation\nlimitations: Locus-selective cell-culture result; promoter demethylation did not automatically activate every affected gene.\nexposure: 100 µg/mL L-ascorbic acid 2-phosphate (A8960), medium replaced daily; 12-h and 72-h sampling.\ncross_nutrient: false\nevidence_location: Figure 2; resistant-region analysis\n[c-reg-blaschke] Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells. (2013). https://pubmed.ncbi.nlm.nih.gov/23812591/ DOI: 10.1038/nature12362","model_system":"Mouse Oct4-GiP ESCs in feeder-free 2i/LIF medium; DNA dot blot and hydroxymethyl-DNA immunoprecipitation; mC-DIP sequencing/qPCR and bisulfite validation","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [c-reg-blaschke] Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells. (2013). https://pubmed.ncbi.nlm.nih.gov/23812591/ DOI: 10.1038/nature12362","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"fa811221-13bd-5c10-adc1-eaf097c7703c","stable_key":"import-cb568d28-484a-5c2e-9fcc-2d780358e514","title":"Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"b7fd83f956abb81855f2ea23199ba14e465cd91f4a2ac560277ec21ddafd7bfc","revision_id":"6cde9bbb-d712-5746-82a6-85b144253efa","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}