Abstract
Glycosylation is a metabolic pathway consisting of the enzymatic modification of proteins and lipids through the stepwise addition of sugars that gives rise to glycoconjugates. To determine the full complement of glycoconjugates that cells produce (the glycome), a variety of genes are involved, many of which are regulated by DNA methylation. The aim of the present review is to briefly describe some relevant examples of glycosylation-related genes whose DNA methylation has been implicated in their regulation and to focus on the intriguing case of a glycosyltransferase gene (B3GALT5). Aberrant promoter methylation is frequently at the basis of their modulation in cancer, but in the case of B3GALT5, at least two promoters are involved in regulation, and a complex interplay is reported to occur between transcription factors, chromatin remodelling and DNA methylation of typical CpG islands or even of other CpG dinucleotides. Transcription of the B3GALT5 gene underwent a particular evolutionary fate, so that promoter hypermethylation, acting on one transcript, and hypomethylation of other sequences, acting on the other, cooperate on one gene to obtain full cancer-associated silencing. The findings may also help in unravelling the complex origin of serum CA19.9 antigen circulating in some patients.
Highlights
The extreme complexity of multicellular organisms requires that their molecular and cellular interactions are tuned with absolute precision in terms of temporal and spatial organization
Glycosylation is a metabolic pathway consisting of the enzymatic modification of proteins and lipids through the stepwise addition of sugars that gives rise to the glycoconjugates: glycoproteins, glycolipids and proteoglycans
The aim of the present review is to briefly describe some relevant examples of glycogenes controlled through DNA methylation and to focus on the intriguing case of a glycosyltransferase gene, the regulation of which involves at least two promoters and a complex interplay between transcription factors, chromatin remodelling, DNA methylation of typical CpG islands or even of other CpG
Summary
The extreme complexity of multicellular organisms requires that their molecular and cellular interactions are tuned with absolute precision in terms of temporal and spatial organization. The aim of the present review is to briefly describe some relevant examples of glycogenes controlled through DNA methylation and to focus on the intriguing case of a glycosyltransferase gene, the regulation of which involves at least two promoters and a complex interplay between transcription factors, chromatin remodelling, DNA methylation of typical CpG islands or even of other CpG dinucleotides. It appears responsible for efficient cancer-associated silencing and probably fine tissue-specific expression of a galactosyltransferase enzyme isoform (B3GALT5), which underwent a particular evolutionary fate
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