Physiological and pathological implications of 5-hydroxymethylcytosine in diseases

Abstract

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.

Endonuclease G promotes mitochondrial genome cleavage and replication

“…We hypothesise that this cleavage reaction may be initiated by demethylation processes at non-CpG sites, providing a potential biological role for the yet unknown function of 5hmC accumulation in mtDNA. Since, changes in 5hmC mtDNA methylation are associated with a wide range of pathological conditions such as cancer, neurodegeneration and aging [ 65 , 93 ], our observations broaden the current understanding of the development of these diseases and highlight EndoG as a potential target for future therapies.…”

Genome-wide 5-hydroxymethylcytosine patterns in human spermatogenesis are associated with semen quality

“…The use of epigenetic analysis for categorization of infertile patients is supposed to significantly improve diagnostic approaches in the field of male reproduction [ 52 , 53 ]. Moreover, understanding the mechanisms involved in epigenetic alterations opens the way for targeted treatment of pathological conditions [ 54 , 55 ]. We believe that our findings are potentially significant for diagnosis and treatment of male infertility.…”

5-Hydroxymethylcytosine (5hmC), or How to Identify Your Favorite Cell

“…Whether related or not to the preservation of cell identity, this oxidative form of methylated cytosine is emerging as a novel marker in many disorders [107]. Studies assessing 5mC and 5hmC content in different neurodegenerative pathologies, including Alzheimer's and Huntington's diseases, haven been reviewed in past years [108].…”