Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.37 (DNA methyltransferase)
 4,983 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To gain further insight into the basis for the extended longevity and delayed aging of Snell dwarf (dw/dw) mice, we have measured levels of expression of 2352 genes in liver of mice at 6 months of age. We find 60 genes for the which the Student's t statistic meets the arbitrary criterion of p <.001, and among these 17 meet the Bonferroni-adjusted significance criterion at p <.05, which corresponds to a nominal value of p <.00002. Using the Bonferroni criterion, we find that dwarf mice show increases in liver mRNA for two mannose-binding lectins, two DNA binding proteins, serum amyloid P component, corticosteroid-binding globulin, and insulin-like growth factor-binding protein 2, as well as decreases in a two phosphodiesterases, a pheromone-binding urinary protein, insulin-like growth factor-I (IGF-I), a calcium-binding protein calgranulin B, a deubiquitinating enzyme, a hydroxysteroid dehydrogenase, a DNA methyltransferase, a glycine transporter, and a placental lactogen. We also use this data set to compare the results of different suggested criteria for evaluating intergroup differences in gene expression. Of the 2352 genes examined, 524 (22%) showed a twofold difference between dwarf and normal mice, but most of these fail to meet the conventional significance criterion of p <.05, let alone criteria that have been adjusted to compensate for multiple comparison artifacts. The list of genes that show reliable differences between dwarf and control animals provides new insights into the range of changes induced by deficiencies in growth hormone, thyroid-stimulating hormone, and prolactin, and it will help to guide further studies of the pathways by which these hormone deficiencies contribute to delayed aging in these mutant mice.
 ...
PMID:Gene expression profile of long-lived snell dwarf mice. 1186 46

Microarray analysis of paired cultures of normal and cancerous urothelial cells revealed differences in cytokeratin and adhesion gene expression. Normal cells expressed autocrine growth factor genes more strongly whereas carcinoma cells were distinguished by concomitant expression of urothelial and epidermal differentiation markers. Expression of SNCG, S100A9 and LCN2 was also enhanced. In other cancers, overexpression of SNCG, LCN2 and S100A4 has been ascribed to DNA hypomethylation. We therefore investigated expression and methylation of SNCG, S100A4, S100A9 and LCN2 in urothelial cancer cell lines and tissues. SNCG and S100A4 were overexpressed in some cancer tissues and cell lines, but downregulated in others, whereas LCN2 and S100A9 were upregulated in few cancer cell lines, but regularly in tissues. Normal and cancerous urothelial cells expressing SNCG lacked promoter methylation. SNCG downregulation was associated with hypermethylation and could be reversed by the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine. S100A4 methylation at regulatory intronic sites and in the promoter region was lowest in leukocytes and fibroblasts, and denser in urothelial cells. Gene expression responded to 5-aza-2'-deoxycytidine. LCN2 promoter methylation was variable and even less consistently related to expression. The S100A9 promoter was partially methylated in nonexpressing cells, but 5-aza-2'-deoxycytidine had no effect. Our data indicate that SNCG methylation is cell type-specific and the gene is hypermethylated in some urothelial cancers. S100A4, S100A9 and LCN2 are genes with moderate CpG-density that show a less stringent relationship between DNA methylation and gene expression. Therefore, changes in methylation of these genes in cancer should be interpreted cautiously.
 ...
PMID:Relationship of SNCG, S100A4, S100A9 and LCN2 gene expression and DNA methylation in bladder cancer. 1880 90