Vitamin D has wide regulatory effects on histone demethylase genes.
Cell Cycle
; 11(6): 1081-9, 2012 Mar 15.
Article
em En
| MEDLINE
| ID: mdl-22370479
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 miR200b and miR200c, 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Vitamina D
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Regulação Neoplásica da Expressão Gênica
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Epigênese Genética
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Histona Desmetilases com o Domínio Jumonji
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article