{"id":"c2ae2c39-ee52-53fb-ad0a-043a372ebe07","stable_key":"f992b796-377d-53bf-a39b-7e5d41dbe194:b5-met-acly-hct-histones","predicate":"silencing_reduces","statement":"ACLY silencing reduced acetylation of the core histones assayed in HCT116 cells.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"f893215f-daeb-5bc6-b063-96935a3780a8","mechanism_event_label":"Histone acetylation depended partly on this source of acetyl-CoA in colon-cancer cells.","subject":{"id":"5064bef8-55ab-5b0e-ba54-581e14231ebe","slug":"acly","display_name":"Human ATP-citrate lyase / ACLY","entity_type_key":"protein"},"object":{"id":"ec8d4882-1462-5107-8400-367298f439e1","slug":"histone-acetylation","display_name":"Core histone lysine acetylation","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"f893215f-daeb-5bc6-b063-96935a3780a8","stable_key":"f992b796-377d-53bf-a39b-7e5d41dbe194:b5-met-acly-hct-histones-event","event_type":"biochemical_relationship","label":"Histone acetylation depended partly on this source of acetyl-CoA in colon-cancer cells.","description":"ACLY silencing reduced acetylation of the core histones assayed in HCT116 cells.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"b7ed6e4c-e560-5cee-b68f-895f21862e6f","slug":"acetyl-coa","display_name":"Acetyl-CoA","entity_type_key":"small_molecule"},"role":"acetyl_group_donor","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"44399a64-dd8a-5818-a863-b3389c6adf37","slug":"protein-bound-lysine","display_name":"Protein-bound lysine residue","entity_type_key":"protein_state"},"role":"protein_acceptor_residue","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"1c54abac-4dfd-5303-b0f4-37945245e18e","slug":"citrate","display_name":"Citrate","entity_type_key":"small_molecule"},"role":"ACLY_carbon_substrate","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"5064bef8-55ab-5b0e-ba54-581e14231ebe","slug":"acly","display_name":"Human ATP-citrate lyase / ACLY","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"ec8d4882-1462-5107-8400-367298f439e1","slug":"histone-acetylation","display_name":"Core histone lysine acetylation","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"cross_nutrient","value_text":"true","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_location","value_text":"BioC text lines 11, 17, 51; Fig. 2A,E","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"ACLY siRNA versus control","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"72-hour siRNA treatment.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Tubulin acetylation was not comparably reduced. This is a source-specific cellular result, not a universal block of protein acetylation. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"pantothenate","display_name":"Pantothenate (vitamin B5)","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Histone acetylation depended partly on this source of acetyl-CoA in colon-cancer cells.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[b5-met-chromatin2009] ATP-citrate lyase links cellular metabolism to histone acetylation. (2009). https://pubmed.ncbi.nlm.nih.gov/19461003/ DOI: 10.1126/science.1164097","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"HCT116 cells and acid-extracted histones","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":"dbf499d4-b441-517d-919e-6343980c5f25","evidence_kind":"source_excerpt","locator":"Lines 991-1003","start_line":991,"end_line":1003,"excerpt":"### b5-met-acly-hct-histones\nACLY silencing reduced acetylation of the core histones assayed in HCT116 cells.\nCondition category: machinery_impairment\nnutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Histone acetylation depended partly on this source of acetyl-CoA in colon-cancer cells.\norganism: Homo sapiens\ntissue_or_cell_type: HCT116 cells and acid-extracted histones\nexperimental_model: ACLY siRNA versus control\nlimitations: Tubulin acetylation was not comparably reduced. This is a source-specific cellular result, not a universal block of protein acetylation. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation.\nexposure: 72-hour siRNA treatment.\ncross_nutrient: true\nevidence_location: BioC text lines 11, 17, 51; Fig. 2A,E\n[b5-met-chromatin2009] ATP-citrate lyase links cellular metabolism to histone acetylation. (2009). https://pubmed.ncbi.nlm.nih.gov/19461003/ DOI: 10.1126/science.1164097","model_system":"ACLY siRNA versus control","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [b5-met-chromatin2009] ATP-citrate lyase links cellular metabolism to histone acetylation. 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