{"id":"a923aa0b-3e29-560b-8b84-2e1e5734704a","stable_key":"182336c6-ed36-5ec6-8a09-25c31096262e:dim-hdac-cycle","predicate":"promotes_in_model","statement":"Class I HDAC depletion was accompanied by increased p21/p27 expression and G2 cell-cycle arrest.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"e52b98b5-1add-56b6-8898-042b2b4f5646","mechanism_event_label":"Changing chromatin regulators connected to cell-cycle control.","subject":{"id":"6009bdd4-f1b5-5867-b5c3-cdf7c9645cd0","slug":"dim","display_name":"3,3'-Diindolylmethane / DIM","entity_type_key":"small_molecule"},"object":{"id":"00c13c93-8a93-5dec-87fb-23e8bdeb1823","slug":"cell-cycle-g2-arrest","display_name":"Cell-cycle arrest in G2","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"e52b98b5-1add-56b6-8898-042b2b4f5646","stable_key":"182336c6-ed36-5ec6-8a09-25c31096262e:dim-hdac-cycle-event","event_type":"biochemical_relationship","label":"Changing chromatin regulators connected to cell-cycle control.","description":"Class I HDAC depletion was accompanied by increased p21/p27 expression and G2 cell-cycle arrest.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"81341cb2-5b47-5770-b3ff-c502382c7343","slug":"cdkn1a","display_name":"Human p21 / CDKN1A","entity_type_key":"protein"},"role":"increased_regulator","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"d2e9d8af-dafd-57d1-91a8-6638b2c4495a","slug":"cdkn1b","display_name":"Human p27 / CDKN1B","entity_type_key":"protein"},"role":"increased_regulator","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"6009bdd4-f1b5-5867-b5c3-cdf7c9645cd0","slug":"dim","display_name":"3,3'-Diindolylmethane / DIM","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"00c13c93-8a93-5dec-87fb-23e8bdeb1823","slug":"cell-cycle-g2-arrest","display_name":"Cell-cycle arrest in G2","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/dim-research/20068155.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"bbb7efbd817b44da2771c9dac2c27d0bf4fe3db97ad9452a93eefc97319ebab9\", \"start_char\": 0, \"end_char\": 862, \"text_sha256\": \"bbb7efbd817b44da2771c9dac2c27d0bf4fe3db97ad9452a93eefc97319ebab9\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Protein degradation and cell-cycle studies","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"DIM; proteasome-mediated protein depletion","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Preclinical concentration/model dependence. The mechanism is loss of HDAC protein, not established direct inhibition of every HDAC catalytic site.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"dim","display_name":"3,3'-Diindolylmethane / DIM","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Human colon-cancer cells and xenografts","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Changing chromatin regulators connected to cell-cycle control.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[dim-p20068155] Chemopreventive agent 3,3'-diindolylmethane selectively induces proteasomal degradation of class I histone deacetylases. (2010). https://pubmed.ncbi.nlm.nih.gov/20068155/ DOI: 10.1158/0008-5472.can-09-1924","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Class I HDAC regulation","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"2084dca0-9eb5-5096-8516-cf08893d8965","evidence_kind":"source_excerpt","locator":"Lines 1416-1427","start_line":1416,"end_line":1427,"excerpt":"### dim-hdac-cycle\nClass I HDAC depletion was accompanied by increased p21/p27 expression and G2 cell-cycle arrest.\nCondition category: normal\nnutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Changing chromatin regulators connected to cell-cycle control.\norganism: Human colon-cancer cells and xenografts\ntissue_or_cell_type: Class I HDAC regulation\nexperimental_model: Protein degradation and cell-cycle studies\nlimitations: Preclinical concentration/model dependence. The mechanism is loss of HDAC protein, not established direct inhibition of every HDAC catalytic site.\nexposure: DIM; proteasome-mediated protein depletion\nevidence_span: {\"source_cache\": \"artifacts/dim-research/20068155.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"bbb7efbd817b44da2771c9dac2c27d0bf4fe3db97ad9452a93eefc97319ebab9\", \"start_char\": 0, \"end_char\": 862, \"text_sha256\": \"bbb7efbd817b44da2771c9dac2c27d0bf4fe3db97ad9452a93eefc97319ebab9\"}\n[dim-p20068155] Chemopreventive agent 3,3'-diindolylmethane selectively induces proteasomal degradation of class I histone deacetylases. (2010). https://pubmed.ncbi.nlm.nih.gov/20068155/ DOI: 10.1158/0008-5472.can-09-1924","model_system":"Protein degradation and cell-cycle studies","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [dim-p20068155] Chemopreventive agent 3,3'-diindolylmethane selectively induces proteasomal degradation of class I histone deacetylases. (2010). https://pubmed.ncbi.nlm.nih.gov/20068155/ DOI: 10.1158/0008-5472.can-09-1924","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"b6d70682-97f9-5893-a03c-f9f88836033c","stable_key":"import-182336c6-ed36-5ec6-8a09-25c31096262e","title":"Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug 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":"31e14060de904976d2f5d439f2bc9c8a99a72d34626c562c78429025e050d404","revision_id":"611094c1-a9cf-5b9b-b255-ac70b571696a","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}