The effect of the epigenome on the Vitamin D Receptor target genes
DOI:
https://doi.org/10.26481/marble.2015.v6.371Abstract
Background. Humans produce vitamin D3 by exposure to sunlight that includes ultraviolet B (UVB) radiation, but also via the intake of nutrients. In the body, the Vitamin D3 is converted to its active form, which is called 1, 25(OH)2D3. This can bind to the Vitamin D Receptor (VDR), which is located on several genes which are called the VDR target genes. Objective. The present study investigated which genes are regulated by the 1, 25(OH)2D3 and checked whether the epigenetic modifications are measured in two cell lines within the ENCODE project. The data of the epigenetic modifications will be linked to the promoter regions of the VDR target genes. In this way the epigenetic control of the VDR target genes could be investigated in more detail. Methods. The human VDR target genes were identified with an extensive literature search. The promoter regions of the VDR target genes were found with Genomatix. Two types of epigenetic modifications, DNA methylation and histone modification, which were determined in two cell lines, IMR90 and H1ESC, in the ENCODE project were linked to the promoter regions of the VDR target genes. In the network analysis program Cytoscape the VDR target genes and the measured epigenetic modifications were integrated and visualized in an epigenetics-VDR target genes network. Results. In total 185 VDR target genes were found in 25 literature papers. There were 528 promoter regions in the 185 VDR target genes identified. In the H1ESC were 445 histone modifications linked to the VDR target gene promoters and in the IMR90 were 259 histone modifications linked to the VDR target gene promoters. In the IMR90 were 158 promoter regions with a DNA methylation region and in the H1ESC were this 177 promoter regions with a DNA methylation region. In the combined network of DNA methylation and histone modifications were in the IMR90 99 genes and in the H1ESC 111 genes selected. Conclusion. The epigenetics-VDR target genes network can be used in further research to understand the role of the epigenetic control of the VDR target genes.References
Fetahu IS, Hobaus J, Kallay E. Vitamin D and the epigenome. Front Physiol. 2014;5:164.
Siggens L, Ekwall K. Epigenetics, chromatin and genome organization: recent advances from the ENCODE project. J Intern Med. 2014;276(3):201-14.
Simmons D. Epigenetic Influences and Disease. Nature Education. 2008;1(1):6. Bendik I, Friedel A, Roos FF, Weber P, Eggersdorfer M. Vitamin D: a critical and essential micronutrient for human health. Front Physiol. 2014;5:248.
Deeb KK, Trump DL, Johnson CS. Vitamin D signaling pathways in cancer: potential for anticancer therapeutics. Nat Rev Cancer. 2007;7(9):684-700.
Bouillon R, Carmeliet G, Lieben L, Watanabe M, Perino A, Auwerx J, et al. Vitamin D and energy homeostasis: of mice and men. Nat Rev Endocrinol. 2014;10(2):79-87.
Expression Atlas [http://www.ebi.ac.uk/gxa/genes/ENSG00000111424]. 2015.
Gene2Promoter [http://www.genomatix.de/online_help/help_eldorado/Gene2Promoter_Intro.html]. 2015.
Kuzmichev A, Nishioka K, Erdjument-Bromage H, Tempst P, Reinberg D. Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein. Genes Dev. 2002;16(22):2893-905.
Rougeulle C, Chaumeil J, Sarma K, Allis CD, Reinberg D, Avner P, et al. Differential histone H3 Lys-9 and Lys-27 methylation profiles on the X chromosome. Mol Cell Biol. 2004;24(12):5475-84.
Peterson C. Histone Modification Table. Cell Signaling Technology. 2007.
Science WIo. GeneCards Human Genome Database. 2015.
Philips T. The Role of Methylation in Gene Expression. Nat Educ. 2008;1(1):116.
