Control of Glycosylation-Related Genes by DNA Methylation: the Intriguing Case of the B3GALT5 Gene and Its Distinct Promoters

Biology

Marco Trinchera²  Aida Zulueta¹  Anna Caretti¹ 

[1] Department of Health Sciences, San Paolo Hospital, University of Milan, 20142 Milano, Italy; E-Mails:;Department of Medicine Clinical and Experimental (DMCS), University of Insubria, 21100 Varese, Italy

关键词: DNA methylation;    regulation of gene expression;    cancer;    glycoconjugates;   

DOI  :  10.3390/biology3030484

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.