Functional aspects of cytidine-guanosine dinucleotides and their locations in genes

Abstract

Originally, the finding of a particular distribution of cytidine-guanosine dinucleotides (CpGs) in genomic DNA was considered to be an interesting structural feature of eukaryotic genome organization. Despite a global depletion of CpGs, genes are frequently associated with CpG clusters called CpG islands (CGIs). CGIs are prevalently unmethylated but often found methylated in pathologic situations. On the other hand, CpGs outside of CGIs are generally methylated and are found mainly in the heterochromatic fraction of the genome. Hypomethylation of those CpGs is associated with genomic instability in malignancy. Additionally, CpG-rich and CpG-poor regions, as well as CpG-shores, are defined. Usually, the methylation status inversely correlates with gene expression. Methylation of CpGs, as well as demethylation and generation of hydroxmethyl-cytosines, is strictly regulated during development and differentiation. This review deals with the relevance of the organizational features of CpGs and their relation to each other.

DMSO is a strong inducer of DNA hydroxymethylation in pre-osteoblastic MC3T3-E1 cells

“…1,10,47-49). This mechanism was suggested for active DNA demethylation in Xenopus laevis oocytes 7 and in embryos of zebrafish 8 .…”

“…Recently, an active DNA-demethylation process has been shown by oxidative modification of 5-mCs to 5-hmCs by members of the TET gene family with further involvement of the GADD45 gene family, which is responsible for nucleotide and base excision repair (for a review see refs. 1 , 10 , 47 - 49 ). This mechanism was suggested for active DNA demethylation in Xenopus laevis oocytes 7 and in embryos of zebrafish.…”

“…One CpG-rich region is localized at 2.6 kb and the second one at 30 bp upstream from the Fas transcriptional start site (TSS). 1 , 4 , 34 As shown in Figure 13 , of the Dlx5 promoter region, a fragment was selected with an overall CpG content of 51%. It starts at 1049 bp upstream from the TSS and extends to 60 bp of the first exon.…”

“…Therewith it is implicated in cell and tissue development and pathogenesis 1 - 3 such as cellular differentiation and cancer development, respectively. For example, it has been demonstrated that suppression of the pro-apoptotic gene Fas via promoter methylation is an essential mechanism for the generation of RAS transformed tumor cells 4 .…”

“…Methylation of cytosine-guanine dinucleotides (CpGs) on DNA is an important epigenetic mechanism involved in the selective regulation of gene expression and in the stabilization of chromatin. Therewith it is implicated in cell and tissue development and pathogenesis 1 - 3 such as cellular differentiation and cancer development, respectively. For example, it has been demonstrated that suppression of the pro-apoptotic gene Fas via promoter methylation is an essential mechanism for the generation of RAS transformed tumor cells.…”