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Vitamin D has wide regulatory effects on histone modifying enzymes in human colon cancer cells

AuthorsBarbáchano, Antonio ; Pereira, Fábio; Fernández-Barral, A. ; Ferrer-Mayorga, Gemma ; Muñoz Terol, Alberto ; Larriba, María Jesús
Issue Date2014
PublisherSociedad Española de Bioquímica y Biología Molecular
CitationXXXVII Congreso SEBBM (2014)
AbstractVitamin D3 is obtained from the diet or mainly synthesized in the skin and is converted into the active metabolite 1alpha, 25-dihydroxyvitamin D3 (1,25(OH)2D3). Epidemiological data suggest a protective role of vitamin D against several neoplasias, particularly colorectal cancer. 1,25(OH)2D3 is a major regulator of gene expression. Histones are subject to posttranslational modifications including methylation, acetylation and others. Misregulation of histone modifi cations alters gene expression and cell phenotype, which may contribute to cancer initiation, progression and/or metastasis. We found that 1,25(OH)2D3has a wide regulatory action on the expression of genes coding for histone demethylases of the Jumonji C domain and lysine-specifi c demethylase families (Pereira et al., 2011; 2012). Notably, 1,25(OH)2D3induces the expression of the histone demethylase JMJD3/KDM6B that specifi cally demethylates the lysine 27 of histone H3 (H3K27) and has tumour suppressor activity. We found that the induction of JMJD3 is necessary for the adequate gene regulatory, antiproliferative, and prodifferentiation actions of 1,25(OH)2D3 in human colon cancer cells. Conversely, 1,25(OH)2D3 inhibits the expression of several Polycomb group proteins that participate in the Polycomb repressive complexes (PRC) 1 and 2, which are responsible for H3K27 methylation and promote tumorigenesis. The inhibition of PRC2 activity by DZNep potentiates the gene regulatory action of 1,25(OH)2D3 and also its effects on colon cancer cell proliferation and differentiation. Thus, 1,25(OH)2D3 exerts an ample regulatory effect on the expression of histone modifying enzymes involved in epigenetic regulation that, in turn, mediate 1,25(OH)2D3 actions on gene expression and cell phenotype in colon cancer.
DescriptionResumen del póster presentado al XXXVII Congreso de la Sociedad Española de Bioquímica y Biología Molecular, celebrado en Granada del 9 al 12 de septiembre de 2014.
Appears in Collections:(IIBM) Comunicaciones congresos
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