Physiological and pathological implications of 5-hydroxymethylcytosine in diseases

Gene expression is the prerequisite of proteins. Diverse stimuli result in alteration of gene expression profile by base substitution for quite a long time. However, during the past decades, accumulating studies proved that bases modification is involved in this process. CpG islands (CGIs) are DNA fragments enriched in CpG repeats which mostly locate in promoters. They are frequently modified, methylated in most conditions, thereby suggesting a role of methylation in profiling gene expression. DNA methylation occurs in many conditions, such as cancer, embryogenesis, nervous system diseases etc. Recently, 5-hydroxymethylcytosine (5hmC), the product of 5-methylcytosine (5mC) demethylation, is emerging as a novel demethylation marker in many disorders. Consistently, conversion of 5mC to 5hmC has been proved in many studies. Here, we reviewed recent studies concerning demethylation via 5hmC conversion in several conditions and progress of therapeutics-associated with it in clinic. We aimed to unveil its physiological and pathological significance in diseases and to provide insight into its clinical application potential.