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dc.contributor.author | Pereira, Fábio | - |
dc.contributor.author | Barbáchano, Antonio | - |
dc.contributor.author | Silva, Javier | - |
dc.contributor.author | Bonilla, Félix | - |
dc.contributor.author | Campbell, Moray J. | - |
dc.contributor.author | Muñoz Terol, Alberto | - |
dc.contributor.author | Larriba, María Jesús | - |
dc.date.accessioned | 2013-05-31T09:27:26Z | - |
dc.date.available | 2013-05-31T09:27:26Z | - |
dc.date.issued | 2011 | - |
dc.identifier | doi: 10.1093/hmg/ddr399 | - |
dc.identifier | issn: 0964-6906 | - |
dc.identifier | e-issn: 1460-2083 | - |
dc.identifier.citation | Human Molecular Genetics 20(23): 4655-4665 (2011) | - |
dc.identifier.uri | http://hdl.handle.net/10261/77254 | - |
dc.description | El pdf es la versión pre-print. | - |
dc.description.abstract | KDM6B/JMJD3 is a histone H3 lysine demethylase with an important gene regulatory role in development and physiology. Here, we show that human JMJD3 expression is induced by the active vitamin D metabolite 1¿,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) and that JMJD3 modulates the gene regulatory action of this hormone. 1,25(OH)(2)D(3) activates the JMJD3 gene promoter and increases the level of JMJD3 RNA in human cancer cells. JMJD3 upregulation was strictly dependent on vitamin D receptor (VDR) expression and was abolished by cycloheximide. In SW480-ADH colon cancer cells, JMJD3 knockdown or expression of an inactive mutant JMJD3 fragment decreased the induction by 1,25(OH)(2)D(3) of several target genes and of an epithelial adhesive phenotype. Moreover, JMJD3 knockdown upregulated the epithelial-to-mesenchymal transition inducers SNAIL1 and ZEB1 and the mesenchymal markers fibronectin and LEF1, while it downregulated the epithelial proteins E-cadherin, Claudin-1 and Claudin-7. Additionally, JMJD3 knockdown abolished the nuclear export of ß-catenin and the inhibition of ß-catenin transcriptional activity caused by 1,25(OH)(2)D(3). Importantly, the expression of JMJD3 correlated directly with that of VDR and inversely with that of SNAI1 in a series of 96 human colon tumours. Our results indicate for the first time that an epigenetic gene coding for a histone demethylase such as JMJD3 is a VDR co-target that partially mediates the effects of 1,25(OH)(2)D(3) on human colon. | - |
dc.description.sponsorship | This work was supported by grants of the Ministerio de Ciencia e Innovación of Spain (SAF2010-18302 to A.M., SAF2010-20750 to F.B.); and the Fondo Europeo de Desarrollo Regional-Instituto de Salud Carlos III (RD06/0020/0009 to A.M., RD06/0020/0020 to F.B.). | - |
dc.language.iso | eng | - |
dc.publisher | Oxford University Press | - |
dc.rights | openAccess | - |
dc.title | KDM6B/JMJD3 histone demethylase is induced by vitamin D and modulates its effects in colon cancer cells | - |
dc.type | artículo | - |
dc.identifier.doi | 10.1093/hmg/ddr399 | - |
dc.relation.publisherversion | http://dx.doi.org/10.1093/hmg/ddr399 | - |
dc.date.updated | 2013-05-31T09:27:26Z | - |
dc.description.version | Peer Reviewed | - |
dc.identifier.pmid | 21890490 | - |
dc.type.coar | http://purl.org/coar/resource_type/c_6501 | es_ES |
item.languageiso639-1 | en | - |
item.fulltext | With Fulltext | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.cerifentitytype | Publications | - |
item.grantfulltext | open | - |
item.openairetype | artículo | - |
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KDM6B-JMJD3.pdf | 386 kB | Adobe PDF | Visualizar/Abrir |
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