title: Vitamin D has wide regulatory effects on histone demethylase genes.
abstract: Vitamin D from the diet or synthesized in the skin upon UV-B irradiation is converted in the organism into the active metabolite 1α,25- dihydroxyvitamin D 3 [1,25(OH) 2D 3, calcitriol], a pleiotropic hormone with wide regulatory actions. The classical model of 1,25(OH)2D3 action implies the activation of the vitamin D receptor, which binds specific DNA sequences in its target genes and modulates their transcription rate. We have recently shown that 1,25(OH) 2D 3 induces the expression of the JMJD3 gene coding for a histone demethylase that is involved in epigenetic regulation. JMJD3 mediates the effects of 1,25(OH) 2D 3 on a subset of target genes and affects the expression of ZEB1, ZEB2 and SNAI1, inducers of epithelial-mesenchymal transition. Novel data indicate that 1,25(OH) 2D 3 has an unanticipated wide regulatory action on the expression of genes coding for histone demethylases of the Jumonji C (JmjC) domain and lysine-specific demethylase (LSD) families. Moreover, JMJD3 knockdown decreases the expression of miR‑200b and miR‑200c, two microRNAs targeting ZEB1 RNA. This may explain the upregulation of this transcription factor found in JMJD3-depleted cells. Thus, 1,25(OH) 2D 3 exerts an ample regulatory effect on the expression of histone-modifying enzymes involved in epigenetic regulation that may mediate its actions on gene transcription and cell phenotype.
authors.affiliation: Department of Cancer Biology, Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Fábio
authors.initials: F
authors.lastname: Pereira
authors.forename: Antonio
authors.initials: A
authors.lastname: Barbáchano
authors.forename: Prashant K
authors.initials: PK
authors.lastname: Singh
authors.forename: Moray J
authors.initials: MJ
authors.lastname: Campbell
authors.forename: Alberto
authors.initials: A
authors.lastname: Muñoz
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Larriba
mesh_terms: D000818:Animals; D001665:Binding Sites; D002117:Calcitriol / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006657:Histones / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D063151:Polycomb Repressive Complex 2; D012313:RNA / Q000235:genetics / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014807:Vitamin D / Q000235:genetics / Q000378:metabolism*; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D006657:Histones; D018398:Homeodomain Proteins; C547777:JARID2 protein, human; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; D018167:Receptors, Calcitriol; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; D014807:Vitamin D; D012313:RNA; D056484:Jumonji Domain-Containing Histone Demethylases; C524220:KDM6B protein, human; D063151:Polycomb Repressive Complex 2; D002117:Calcitriol