{"id":"6d61879b-9408-5bbd-b863-bb0633c4828a","stable_key":"1deb434a-3547-51a0-a038-87b1ce79ec38:vdm-calcitriol-rankl-distal-enhancer","predicate":"increases_expression","statement":"Calcitriol activated mouse Rankl transcription through distal VDR/RXR-associated regulatory regions, including a functional element about 76 kb upstream.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"5dc2ed69-290c-5cdb-8e25-ebf6c79579e6","mechanism_event_label":"Active vitamin D can induce the osteoclast-development signal RANKL through distant DNA control regions.","subject":{"id":"f5156c24-108f-5746-b114-ed764e79a3f4","slug":"calcitriol","display_name":"Calcitriol","entity_type_key":"small_molecule"},"object":{"id":"de7ad036-388f-596d-8766-72afe51b4a67","slug":"tnfsf11","display_name":"RANK ligand / TNFSF11","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"5dc2ed69-290c-5cdb-8e25-ebf6c79579e6","stable_key":"1deb434a-3547-51a0-a038-87b1ce79ec38:vdm-calcitriol-rankl-distal-enhancer-event","event_type":"biochemical_relationship","label":"Active vitamin D can induce the osteoclast-development signal RANKL through distant DNA control regions.","description":"Calcitriol activated mouse Rankl transcription through distal VDR/RXR-associated regulatory regions, including a functional element about 76 kb upstream.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"f5156c24-108f-5746-b114-ed764e79a3f4","slug":"calcitriol","display_name":"Calcitriol","entity_type_key":"small_molecule"},"role":"ligand","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"d725020b-bacc-5e90-b370-cda246025c91","slug":"vdr","display_name":"Vitamin D receptor / VDR","entity_type_key":"protein"},"role":"DNA-binding-receptor","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"7dc1ce11-f208-5187-95d9-96b07927df6a","slug":"rxra","display_name":"Retinoid X receptor alpha","entity_type_key":"protein"},"role":"heterodimer-partner","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"caa5f891-3bee-5acc-bbff-b99c4037d58e","slug":"rxra-vdr","display_name":"RXR alpha-VDR heterodimer","entity_type_key":"protein_complex"},"role":"receptor-complex","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"de7ad036-388f-596d-8766-72afe51b4a67","slug":"tnfsf11","display_name":"RANK ligand / TNFSF11","entity_type_key":"protein"},"role":"regulated-osteoclastogenic-protein","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"e359bc15-e675-5d83-b0fe-1d70814e130b","slug":"calcium-ion","display_name":"Calcium ion","entity_type_key":"ion"},"role":"bone-mineral-context","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"Vitamin D–calcium–phosphate regulation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_locator","value_text":"Abstract: reported experimental results","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_scope","value_text":"D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Mouse osteoblastic cells; VDR/RXR ChIP-chip, reporter mutagenesis and transcriptional assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Calcitriol-treated cell and reporter systems; dose and time vary by experiment and are not specified in the retrieved abstract.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Enhancer activation is distinct from a fracture outcome. The human and mouse regulatory landscapes are not asserted to be identical.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient","value_text":"Vitamin D2 and D3","comparator":null,"unit":null,"notes":"","entity":{"slug":"vitamin-d","display_name":"Vitamin D2 and D3","entity_type_key":"chemical_species"}},{"dimension":"nutrient_topic","value_text":"Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"vitamin-d","display_name":"Vitamin D2 and D3","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Mus musculus","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Active vitamin D can induce the osteoclast-development signal RANKL through distant DNA control regions.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[vdm-meyer2006rankl] Activation of receptor activator of NF-kappaB ligand gene expression by 1,25-dihydroxyvitamin D3 is mediated through multiple long-range enhancers. (2006). https://pubmed.ncbi.nlm.nih.gov/16914732/ DOI: 10.1128/mcb.00353-06","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Osteoblastic cell chromatin","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"1dfa9e97-cedb-52c7-9f70-5eff95cc2b80","evidence_kind":"source_excerpt","locator":"Lines 841-855","start_line":841,"end_line":855,"excerpt":"### vdm-calcitriol-rankl-distal-enhancer\nCalcitriol activated mouse Rankl transcription through distal VDR/RXR-associated regulatory regions, including a functional element about 76 kb upstream.\nCondition category: normal\nnutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Active vitamin D can induce the osteoclast-development signal RANKL through distant DNA control regions.\norganism: Mus musculus\ntissue_or_cell_type: Osteoblastic cell chromatin\nexperimental_model: Mouse osteoblastic cells; VDR/RXR ChIP-chip, reporter mutagenesis and transcriptional assays\nlimitations: Enhancer activation is distinct from a fracture outcome. The human and mouse regulatory landscapes are not asserted to be identical.\nexposure: Calcitriol-treated cell and reporter systems; dose and time vary by experiment and are not specified in the retrieved abstract.\ncross_nutrient: Vitamin D–calcium–phosphate regulation.\nevidence_locator: Abstract: reported experimental results\nnutrient: Vitamin D2 and D3\nevidence_scope: D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison.\n[vdm-meyer2006rankl] Activation of receptor activator of NF-kappaB ligand gene expression by 1,25-dihydroxyvitamin D3 is mediated through multiple long-range enhancers. (2006). https://pubmed.ncbi.nlm.nih.gov/16914732/ DOI: 10.1128/mcb.00353-06","model_system":"Mouse osteoblastic cells; VDR/RXR ChIP-chip, reporter mutagenesis and transcriptional assays","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [vdm-meyer2006rankl] Activation of receptor activator of NF-kappaB ligand gene expression by 1,25-dihydroxyvitamin D3 is mediated through multiple long-range enhancers. (2006). https://pubmed.ncbi.nlm.nih.gov/16914732/ DOI: 10.1128/mcb.00353-06","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"c95c763c-5b31-5b3f-a2f8-2dfe5ef0d3ca","stable_key":"import-1deb434a-3547-51a0-a038-87b1ce79ec38","title":"Vitamin D2 and D3: 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":"51004bf0d78db6146b8f198b0688a3cc7d4ea9822415a9c034f4c8790fb4e38b","revision_id":"d52ff207-a311-5f24-96f4-462838792db5","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}